Author: "Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC)" - Searchworks@Jio Institute Digital Library Search Results

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251 results on '"Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC)"'

151. Pregnancy with multiple sclerosis

Author: Sandra Vukusic, Christine Lebrun-Frenay, L. Michel, S. Leguy, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Hôpital Pasteur [Nice] (CHU), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Pediatrics, medicine.medical_specialty, Multiple Sclerosis, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Breastfeeding, Fertility, Disease, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Recurrence, medicine, Humans, 030212 general & internal medicine, media_common, Fetus, business.industry, Multiple sclerosis, medicine.disease, 3. Good health, Discontinuation, Clinical Practice, Pregnancy Complications, Neurology, Female, Neurology (clinical), business, Delivery, 030217 neurology & neurosurgery, Disease modifying drugs
Abstract: International audience; Multiple sclerosis (MS) is usually diagnosed between twenty and forty years of age, when people often plan to have children. A lot has been said about the effect of pregnancy on the course of MS. The individual factors responsible for the disease modifying effect of pregnancy are not well determined. Having MS neither affects the fertility or the course of pregnancy itself. During pregnancy, many women find that their symptoms stay the same or even improve. Epidural and spinal analgesia appear to be safe and in general are not contraindicated for patients with MS. The management of disease-modifying treatments (DMTs) in pregnancy is a new issue for consideration in the clinical practice. There is limited information available into the safety of DMT use during pregnancy, especially for the most recent ones. In general, discontinuation of DMTs is recommended before conception to minimize risk of fetal harm. Women with very active MS before pregnancy who stop second-line treatments may show an increase in disease activity during pregnancy. Therefore, it might be discussed to maintain patients on DMTs until pregnancy is confirmed, and sometimes throughout pregnancy, to avoid a rebound of disease activity and severe relapses during pregnancy in very active patients.
Published: 2019
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152. High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice

Author: Laura Couloume, Laetitia Barbin, Emmanuelle Leray, Damien Le Port, Emmanuelle Le Page, Anne Kerbrat, Sandrine Wiertlewski, David-Axel Laplaud, Solenn Ory, L. Michel, Gilles Edan, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), École des Hautes Études en Santé Publique [EHESP] (EHESP), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Rennes] = Neurology [Rennes], Etablissement Français du Sang Bretagne, EFS, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Association ANTARES, MedDay Pharma, Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and EHESP, SCD
Subjects: Adult, medicine.medical_specialty, secondary progressive multiple sclerosis, Multiple Sclerosis, primary progressive multiple sclerosis, effectiveness, Biotin, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, law, Internal medicine, medicine, Humans, Prospective Studies, 10. No inequality, Prospective cohort study, Adverse effect, Progressive multiple sclerosis, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Neurology, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Disease Progression, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), progression, business, 030217 neurology & neurosurgery
Abstract: Background: A recent controlled trial suggested that high-dose biotin supplementation reverses disability progression in patients with progressive multiple sclerosis. Objective: To analyze the impact of high-dose biotin in routine clinical practice on disability progression at 12 months. Methods: Progressive multiple sclerosis patients who started high-dose biotin at Nantes or Rennes Hospital between 3 June 2015 and 15 September 2017 were included in this prospective study. Disability outcome measures, patient-reported outcome measures, relapses, magnetic resonance imaging (MRI) data, and adverse events were collected at baseline, 6, and 12 months. Results: A total of 178 patients were included. At baseline, patients were 52.0 ± 9.4 years old, mean Expanded Disability Status Scale (EDSS) score was 6.1 ± 1.3, mean disease duration was 16.9 ± 9.5 years. At 12 months, 3.8% of the patients had an improved EDSS score. Regarding the other disability scales, scores either remained stable or increased significantly. In total, 47.4% of the patients described stability, 27.6% felt an improvement, and 25% described a worsening. Four patients (2.2%) had a relapse. Of the 74 patients (41.6%) who underwent an MRI, 20 (27.0%) had new T2 lesions, 8 (10.8%) had gadolinium-enhancing lesions. Twenty-five (14%) reported adverse event. Conclusion: In this study, high-dose biotin did not seem to be associated with a clear improvement in disability.
Published: 2019
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153. Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer

Author: Fatima Mechta-Grigoriou, Karin Tarte, Sylvain Baulande, Floriane Pelon, Andrei Zinovyev, Luca Albergante, Gérard Zalcman, Brigitte Bourachot, Sonia Lameiras, Hocine Rachid Hocine, Yann Kieffer, Charles Bernard, Claire Bonneau, Géraldine Gentric, Alice Guyard, Anne Vincent-Salomon, Institut Curie [Paris], Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), INCa-DGOS-4654, Institut National Du Cancer, Scientific council, Fondation pour la Recherche Médicale, Labelisation, Ligue Contre le Cancer, Incentive and Cooperative program, Institut Curie, Grand Prix, Fondation Simone et Cino Del Duca, ANR-10-INBS-09-08, Agence Nationale de la Recherche, PC201317, Institut National de la Sante et de la Recherche Medicale, Grand Prix, Le Cancer du sein, Parlons-en, ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), MINES ParisTech - École nationale supérieure des mines de Paris, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, and PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID
Subjects: 0301 basic medicine, medicine.medical_treatment, In silico, Primary Cell Culture, Datasets as Topic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, T-Lymphocytes, Regulatory, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Single-cell analysis, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer-Associated Fibroblasts, Cell Line, Tumor, Neoplasms, medicine, Tumor Microenvironment, Humans, RNA-Seq, Fibroblast, Immune Checkpoint Inhibitors, medicine.diagnostic_test, Cancer, Immunotherapy, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, Tumor Escape, Single-Cell Analysis, Myofibroblast
Abstract: A subset of cancer-associated fibroblasts (FAP+/CAF-S1) mediates immunosuppression in breast cancers, but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19,000 single CAF-S1 fibroblasts from breast cancer. We validate the five most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extracellular matrix proteins and TGFβ signaling, respectively, are indicative of primary resistance to immunotherapies. Cluster 0/ecm-myCAF upregulates PD-1 and CTLA4 protein levels in regulatory T lymphocytes (Tregs), which, in turn, increases CAF-S1 cluster 3/TGFβ-myCAF cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance. Significance: Our work provides a significant advance in characterizing and understanding FAP+ CAF in cancer. We reached a high resolution at single-cell level, which enabled us to identify specific clusters associated with immunosuppression and immunotherapy resistance. Identification of cluster-specific signatures paves the way for therapeutic options in combination with immunotherapies. This article is highlighted in the In This Issue feature, p. 1241
Published: 2019
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154. Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers

Author: Tessa Dhaeze, Alexandre Prat, Boaz Lahav, Laure Michel, Marc-André Lécuyer, Pierre Duquette, Lyne Bourbonnière, Evelyn Peelen, Camille Grasmuck, Amit Bar-Or, Robert Moumdjian, Marc Charabati, Alain Bouthillier, Jennifer L. Gommerman, Sandra Larouche, Stephanie Zandee, Jorge I. Alvarez, Rui Li, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), University of Pennsylvania [Philadelphia], University of Toronto, Fonds de Recherche du Québec - Santé, Multiple Sclerosis Society of Canada, Canada Research Chairs, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Pennsylvania
Subjects: Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Lymphocyte, Encephalomyelitis, [SDV]Life Sciences [q-bio], Central nervous system, Severity of Illness Index, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Activated-Leukocyte Cell Adhesion Molecule, Animals, Humans, Medicine, Endothelium, ALCAM, 030304 developmental biology, Mice, Knockout, B-Lymphocytes, 0303 health sciences, business.industry, Multiple sclerosis, Experimental autoimmune encephalomyelitis, General Medicine, medicine.disease, Recombinant Proteins, 3. Good health, medicine.anatomical_structure, Blood-Brain Barrier, Immunology, Myelin-Oligodendrocyte Glycoprotein, business, Immunologic Memory, 030217 neurology & neurosurgery
Abstract: International audience; The presence of B lymphocyte-associated oligoclonal immunoglobulins in the cerebrospinal fluid is a classic hallmark of multiple sclerosis (MS). The clinical efficacy of anti-CD20 therapies supports a major role for B lymphocytes in MS development. Although activated oligoclonal populations of pathogenic B lymphocytes are able to traffic between the peripheral circulation and the central nervous system (CNS) in patients with MS, molecular players involved in this migration have not yet been elucidated. In this study, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM/CD166) identifies subsets of proinflammatory B lymphocytes and drives their transmigration across different CNS barriers in mouse and human. We also showcased that blocking ALCAM alleviated disease severity in animals affected by a B cell-dependent form of experimental autoimmune encephalomyelitis. Last, we determined that the proportion of ALCAM+ B lymphocytes was increased in the peripheral blood and within brain lesions of patients with MS. Our findings indicate that restricting access to the CNS by targeting ALCAM on pathogenic B lymphocytes might represent a promising strategy for the development of next-generation B lymphocyte-targeting therapies for the treatment of MS. © 2019 The Authors.
Published: 2019
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155. Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response

Author: Steven H. Kleinstein, Christopher E. Mason, Leandro Venturutti, Christian Steidl, Kenneth B. Hoehn, María T. Calvo-Fernández, Olivier Elemento, Katsuyoshi Takata, Neil L. Kelleher, C. David Allis, Johana Gutierrez, Alexey A. Soshnev, Jude M. Phillip, Wendy Béguelin, Cem Meydan, Martín A. Rivas, Jeannie M. Camarillo, Matt Teater, Ari Melnick, Karin Tarte, Cornell University [New York], Yale University School of Medicine, Rockefeller University [New York], Northwestern University [Evanston], British Columbia, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Weill Medical College of Cornell University [New York], NCI CCSG [P30 CA060553], NCIUnited States Department of Health and Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R35 CA220499, LLS TRP 6572-19, LLS SCOR 7013-17, RO1 CA198089], Damon Runyon Cancer Research Foundation, PhRMA Foundation Post-doctoral Fellowship in Informatics, LLS Career Development Program fellowship, Uehara Memorial FoundationUehara Memorial Foundation, Michael Smith Foundation for Health Research (Career Investigator Award)Michael Smith Foundation for Health Research, Terry Fox Research Institute, Canada LLS, [P41 GM108569], ASH Junior Faculty Scholar Award, Follicular Lymphoma Consortium, Chemotherapy Foundation, NIHUnited States Department of Health and Human ServicesNational Institutes of Health (NIH) - USA [RO1A1104739], Yale School of Medicine [New Haven, Connecticut] (YSM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Cancer Research, Lymphoma, B-Cell, Follicular lymphoma, immune microenvironment, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Biology, Malignant transformation, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, follicular lymphoma, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, EZH2, Lymphoma, Follicular, B cell, B-Lymphocytes, Follicular dendritic cells, Germinal center, Dendritic Cells, medicine.disease, Cellular Reprogramming, Germinal Center, Lymphoma, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Cell Transformation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, epigenetic dysregulation, Reprogramming
Abstract: International audience; Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.
Published: 2019
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156. Increasing life science resources re-usability using Semantic Web technologies

Author: Marine Louarn, Thierry Fest, Fabrice Chatonnet, Anne Siegel, Xavier Garnier, Olivier Dameron, Dynamics, Logics and Inference for biological Systems and Sequences (Dyliss), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Louarn, Marine, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Standardization, [INFO.INFO-WB] Computer Science [cs]/Web, Computer science, 0206 medical engineering, 02 engineering and technology, Reuse, SPARQL, Set (abstract data type), 03 medical and health sciences, [INFO.INFO-DB] Computer Science [cs]/Databases [cs.DB], Semantic Web, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Structure (mathematical logic), 0303 health sciences, Information retrieval, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], [INFO.INFO-WB]Computer Science [cs]/Web, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], computer.file_format, bioinformatics, Pipeline (software), Reference data, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], reproducibility of results, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], computer, 020602 bioinformatics
Abstract: In life sciences, current standardization and integration efforts are directed towards reference data and knowledge bases. However, original studies results are generally provided in non standardized and specific formats. In addition, the only formalization of analysis pipelines is often limited to textual descriptions in the method sections. Both factors impair the results reproducibility, their maintenance and their reuse for advancing other studies. Semantic Web technologies have proven their efficiency for facilitating the integration and reuse of reference data and knowledge bases. We thus hypothesize that Semantic Web technologies also facilitate reproducibility and reuse of life sciences studies involving pipelines that compute associations between entities according to intermediary relations and dependencies. In order to assess this hypothesis, we considered a case-study in systems biology (http://regulatorycircuits.org), which provides tissue-specific regulatory interaction networks to elucidate perturbations across complex diseases. Our approach consisted in surveying the complete set of provided supplementary files to reveal the underlying structure between the biological entities described in the data. We relied on this structure and used Semantic Web technologies (i) to integrate the Regulatory Circuits data, and (ii) to formalize the analysis pipeline as SPARQL queries. Our result was a 335,429,988 triples dataset on which two SPARQL queries were sufficient to extract each single tissuespecific regulatory network.
Published: 2019

157. Large granular lymphocytic and other rare lymphoid leukemias

Author: Thomas P. Loughran, Thierry Lamy, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Virginia [Charlottesville], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and University of Virginia
Subjects: Rare Diseases, Oncology, Clinical Biochemistry, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS, Leukemia, Lymphoid
Abstract: International audience
Published: 2019
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158. Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation

Author: Diane Damotte, Remy Dulery, Olivier Casasnovas, Caroline Regny, Lysa, Guillaume Manson, Adrien Chauchet, Georges Garnier, Emmanuelle Nicolas-Virelizier, Aspasia Stamatoullas, Jean-Marc Schiano, Krimo Bouabdallah, Hervé Ghesquières, Charles Herbaux, Jean-Baptiste Mear, Roch Houot, Marie-Pierre Moles-Moreau, Pauline Brice, Adrian Tempescul, Alain Delmer, Bénédicte Deau, Anna Schmitt, Laurent Dercle, Cécile Borel, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Princesse Grace [Monaco], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département Hématologie (FNCLCC), Centre Léon Bérard [Lyon], CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d’Hématologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Columbia University Medical Center (CUMC), Columbia University [New York], Hopital Saint-Louis [AP-HP] (AP-HP), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Bristol-Myers SquibbBristol-Myers Squibb, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CCSD, Accord Elsevier, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, 0302 clinical medicine, Antineoplastic Agents, Immunological, Risk Factors, Anti pd1, ComputingMilieux_MISCELLANEOUS, Allogenic haematopoietic stem cell transplantation, Hematopoietic Stem Cell Transplantation, Middle Aged, Hodgkin Disease, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], Haematopoiesis, Nivolumab, 030220 oncology & carcinogenesis, Disease Progression, Female, France, Immunotherapy, Stem cell, Checkpoint inhibitors, Adult, medicine.medical_specialty, Adolescent, Risk Assessment, 03 medical and health sciences, Young Adult, Refractory, Internal medicine, medicine, Humans, Transplantation, Homologous, Aged, Retrospective Studies, Anti-PD1, business.industry, Transplantation, 030104 developmental biology, Hodgkin lymphoma, business
Abstract: Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL).We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT.After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT.Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy.
Published: 2019
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159. [Retracted] Trans-silencing effect of the 3'RR immunoglobulin heavy chain enhancer on Igκ transcription at the pro-B cell stage

Author: Yves Denizot, Alexis Saintamand, François Boyer, Jeanne Cook-Moreau, Nour Ghazzaui, Hussein Issaoui, Ophélie Alyssa Martin, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANR-16-CE12-0017,EpiSwitch-3RR,Dissection génétique et fonctionnelle du rôle de la région de contrôle du locus IgH au cours de la commutation isotypique(2016), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Transcriptional Activation, Cellular differentiation, Genes, RAG-1, Immunology, Biology, Regulatory Sequences, Nucleic Acid, RAG-deficient mice, 03 medical and health sciences, Immunoglobulin kappa-Chains, Mice, 0302 clinical medicine, Transcription (biology), Correspondence, medicine, Immunology and Allergy, Gene silencing, Animals, IgH 3’ regulatory region, Gene Silencing, Enhancer, B cell, 030304 developmental biology, Mice, Knockout, 0303 health sciences, B-Lymphocytes, Precursor Cells, B-Lymphoid, Eμ, Cell Differentiation, Molecular biology, Immunoglobulin Class Switching, V(D)J Recombination, Infectious Diseases, medicine.anatomical_structure, Enhancer Elements, Genetic, Retraction Note, Immunoglobulin class switching, knock-out mice, Knockout mouse, Immunoglobulin heavy chain, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin Heavy Chains, Transcriptional enhancer, 030215 immunology
Abstract: The authors have retracted this Correspondence. After the publication of this correspondence, it came to the authors’ attention that the control RAG2−/− mouse was a RAG2−/−γc−/− mouse. This point resulted in the conclusions being considered invalid. The authors apologize to the journal and its readers for any inconvenience caused. https://doi.org/10.1038/s41423-021-00716-6; International audience; The authors have retracted this Correspondence. After the publication of this correspondence, it came to the authors’ attention that the control RAG2−/− mouse was a RAG2−/−γc−/− mouse. This point resulted in the conclusions being considered invalid. The authors apologize to the journal and its readers for any inconvenience caused. https://doi.org/10.1038/s41423-021-00716-6
Published: 2019
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160. Transcriptional dynamics of normal B and malignant B cells differentiation to effector cells

Author: Hipp, Nicolas, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Rennes 1, Céline Delaloy, and STAR, ABES
Subjects: B lymphocyte, [SDV.IMM] Life Sciences [q-bio]/Immunology, Interleukin-2, Bach2, Waldenström, Interleukine-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lymphocytes B
Abstract: Terminal B cell differentiation gives rise to antibody secreting plasma cells and memory B cells. It's a highly controlled process regulated by external inputs which guide B cell fate in the transition from naive B cells through to plasma cell. Here, we identify that IL-2 signaling triggers the plasma cell differentiation programme via the ERK transduction pathway instigating BACH2 repression. Results obtained using expression profiles of individual cells to bypass heterogeneous and asynchronous B cell responses confirm the crucial role of BACH2 regulating human B cell fate decision in a well-defined in vitro model of primary human naive B cell differentiation into plasma cell. My focus was then to study the temporal resolution of transcriptional dynamics following times series single-cell transcriptome analysis that should pinpoints key regulatory events that govern normal plasma cell differentiation in one hand and, on the other hand, the mechanisms that govern the differentiation arrest of plasma cell differentiation responsible for Waldenström disease, a rare incurable neoplasm. Altogether the data confirm the technological feasibility of the experimental strategies and should contribute to a better understanding of the complex mechanisms that control generation of plasma cell. This projec may ultimately help to achieve greater knowledge of the pathological process in Waldeström disease., La différenciation terminale du lymphocyte B est un processus permettant de générer des plasmocytes sécréteurs d’anticorps, ainsi que des lymphocytes B mémoires. Ce processus est fortement régulé grâce à un ensemble de signaux présents dans le micro-environnement dont l'intégration détermine la progression du lymphocyte B vers le stade différencié. Au cours de ce projet, j'ai identifié que la signalisation IL-2 induit le programme de différenciation plasmocytaire par un mécanisme impliquant la voie de transduction ERK et le facteur de transcription BACH2. Ce travail apporte de nouvelles informations sur le rôle crucial de BACH2 dans le contrôle de la différenciation plasmocytaire humaine grâce, notamment, à des approches à l'échelle de la cellule permettant d'appréhender l'hétérogénéité des réponses immunes dans un modèle de différenciation in vitro. J'ai ensuite développé des études transcriptomiques sur cellules uniques pour une meilleure compréhension des mécanismes moléculaires spatiotemporels de la différenciation plasmocytaire normale d'une part, et des mécanismes moléculaires impliqués dans la pathologie de Waldenström résultant d'une différenciation plasmocytaire avortée d'autre part. Mes travaux valident la faisabilité technologique des approches expérimentales développées et ouvrent de nombreuses perspectives d'analyses visant à mieux caractériser la physiopathologie de la maladie de Waldenström.
Published: 2019

161. Dynamique transcriptionnelle de la différenciation normale et pathologique des lymphocytes B naïfs en cellules effectrices

Author: Hipp, Nicolas, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes, Céline Delaloy, and STAR, ABES
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, B lymphocyte, Interleukin-2, Bach2, Waldenström, Interleukine-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lymphocytes B
Abstract: Terminal B cell differentiation gives rise to antibody secreting plasma cells and memory B cells. It's a highly controlled process regulated by external inputs which guide B cell fate in the transition from naive B cells through to plasma cell. Here, we identify that IL-2 signaling triggers the plasma cell differentiation programme via the ERK transduction pathway instigating BACH2 repression. Results obtained using expression profiles of individual cells to bypass heterogeneous and asynchronous B cell responses confirm the crucial role of BACH2 regulating human B cell fate decision in a well-defined in vitro model of primary human naive B cell differentiation into plasma cell. My focus was then to study the temporal resolution of transcriptional dynamics following times series single-cell transcriptome analysis that should pinpoints key regulatory events that govern normal plasma cell differentiation in one hand and, on the other hand, the mechanisms that govern the differentiation arrest of plasma cell differentiation responsible for Waldenström disease, a rare incurable neoplasm. Altogether the data confirm the technological feasibility of the experimental strategies and should contribute to a better understanding of the complex mechanisms that control generation of plasma cell. This projec may ultimately help to achieve greater knowledge of the pathological process in Waldeström disease., La différenciation terminale du lymphocyte B est un processus permettant de générer des plasmocytes sécréteurs d’anticorps, ainsi que des lymphocytes B mémoires. Ce processus est fortement régulé grâce à un ensemble de signaux présents dans le micro-environnement dont l'intégration détermine la progression du lymphocyte B vers le stade différencié. Au cours de ce projet, j'ai identifié que la signalisation IL-2 induit le programme de différenciation plasmocytaire par un mécanisme impliquant la voie de transduction ERK et le facteur de transcription BACH2. Ce travail apporte de nouvelles informations sur le rôle crucial de BACH2 dans le contrôle de la différenciation plasmocytaire humaine grâce, notamment, à des approches à l'échelle de la cellule permettant d'appréhender l'hétérogénéité des réponses immunes dans un modèle de différenciation in vitro. J'ai ensuite développé des études transcriptomiques sur cellules uniques pour une meilleure compréhension des mécanismes moléculaires spatiotemporels de la différenciation plasmocytaire normale d'une part, et des mécanismes moléculaires impliqués dans la pathologie de Waldenström résultant d'une différenciation plasmocytaire avortée d'autre part. Mes travaux valident la faisabilité technologique des approches expérimentales développées et ouvrent de nombreuses perspectives d'analyses visant à mieux caractériser la physiopathologie de la maladie de Waldenström.
Published: 2019

162. Locus suicide recombination actively occurs on the functionally rearranged IgH allele in B- cells from inflamed human lymphoid tissues

Author: Gersende Caron, Fabrice Chatonnet, Emilie Lereclus, Jean-Claude Aldigier, Sandrine Le Noir, Thierry Fest, Sophie Péron, Robin Jeannet, Zeinab Dalloul, Iman Dalloul, Amandine Pignarre, Jeanne Cook-Moreau, Anne Durandy, Michel Cogné, Céline Delaloy, François Boyer, Hend Boutouil, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] (EFS Bretagne), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants to MC from Association pour la Recherche sur le Cancer (PGA120150202338), Agence Nationale de la Recherche (ANR grant 16-CE15-0019-01), Institut National du Cancer (INCa grant #9363), Ligue Nationale contre le Cancer and Région Aquitaine-Limousin-Poitou-Charente., ANR-16-CE15-0019,Ig-MemImpact,Rôle de la classe des Ig / BCR dans les interactions cellulaires supportant la mémoire immune et impact immunopathologique(2016), Bodescot, Myriam, Rôle de la classe des Ig / BCR dans les interactions cellulaires supportant la mémoire immune et impact immunopathologique - - Ig-MemImpact2016 - ANR-16-CE15-0019 - AAPG2016 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Cancer Research, B Cells, Cellular differentiation, Palatine Tonsil, Artificial Gene Amplification and Extension, Regulatory Sequences, Nucleic Acid, QH426-470, Polymerase Chain Reaction, White Blood Cells, Mice, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 0303 health sciences, B-Lymphocytes, Gene targeting, Cell Differentiation, Tonsils, Cell biology, Regulatory sequence, Gene Targeting, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cellular Types, Anatomy, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lymphoid Tissue, Immune Cells, Immunology, Plasma Cells, Immunoglobulins, Receptors, Antigen, B-Cell, Locus (genetics), Biology, Research and Analysis Methods, Affinity maturation, Throat, 03 medical and health sciences, Cytidine Deaminase, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Allele, Antibody-Producing Cells, Molecular Biology Techniques, Gene, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Alleles, 030304 developmental biology, Blood Cells, Biology and Life Sciences, Cell Biology, Memory B cells, Immunoglobulin Switch Region, Immunoglobulin class switching, Genetic Loci, Artificial Genetic Recombination, 030217 neurology & neurosurgery, Neck, Developmental Biology
Abstract: B-cell activation yields abundant cell death in parallel to clonal amplification and remodeling of immunoglobulin (Ig) genes by activation-induced deaminase (AID). AID promotes affinity maturation of Ig variable regions and class switch recombination (CSR) in mature B lymphocytes. In the IgH locus, these processes are under control of the 3’ regulatory region (3’RR) super-enhancer, a region demonstrated in the mouse to be both transcribed and itself targeted by AID-mediated recombination. Alternatively to CSR, IgH deletions joining Sμ to “like-switch” DNA repeats that flank the 3’ super-enhancer can thus accomplish so-called “locus suicide recombination” (LSR) in mouse B-cells. Using an optimized LSR-seq high throughput method, we now show that AID-mediated LSR is evolutionarily conserved and also actively occurs in humans, providing an activation-induced cell death pathway in multiple conditions of B-cell activation. LSR either focuses on the functional IgH allele or is bi-allelic, and its signature is mainly detected when LSR is ongoing while it vanishes from fully differentiated plasma cells or from “resting” blood memory B-cells. Highly diversified breakpoints are distributed either within the upstream (3’RR1) or downstream (3’RR2) copies of the IgH 3’ super-enhancer and all conditions activating CSR in vitro also seem to trigger LSR although TLR ligation appeared the most efficient. Molecular analysis of breakpoints and junctions confirms that LSR is AID-dependent and reveals junctional sequences somehow similar to CSR junctions but with increased usage of microhomologies., Author summary Class switch recombination, initiated by the activation-induced deaminase enzyme rearranges immunoglobulin (Ig) genes in order to replace expression of IgM by IgG, IgA or IgE. A variant form of this event, locus suicide recombination (LSR), was previously reported in mouse B-lymphocytes and simply deletes all functional Ig constant genes, thus terminating B-cell function. This study first demonstrates that the structure of the human Ig heavy chain locus provides an ideal target for LSR, and is thus actively (but transiently) affected by this deletion process at the activated B-cell stage. LSR then yields recombined genes that do not support B-cell survival and which thus becomes almost undetectable among long-lived memory B-cells or plasma cells.
Published: 2019
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163. Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma (vol 32, pg 1258, 2018)

Author: Araf, Shamzah, Wang, Jun, Korfi, Koorosh, Pangault, Celine, Kotsiou, Eleni, Rio-Machin, Ana, Rahim, Tahrima, Heward, James, Clear, Andrew, Iqbal, Sameena, Davies, Jeff K., Johnson, Peter, Calaminici, Maria, Montoto, Silvia, Auer, Rebecca, Chelala, Claude, Gribben, John G., Graham, Trevor A., Fest, Thierry, Fitzgibbon, Jude, Okosun, Jessica, Queen Mary University of London (QMUL), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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164. Exploring T[FH] subsets involvement in Multiple Sclerosis course

Author: Morille, J., Rodriguez, S., Thomas, P., Garcia, A., Berthelot, L., Nicot, A., Brouard, S., Laplaud, D.A., Michel, L., Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire SITI [CHU Rennes], Etablissement français du sang [Rennes] (EFS Bretagne)-CHU Pontchaillou [Rennes], Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Le Bihan, Sylvie
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2019

165. Une anémie microcytaire sidéroblastique carentielle traitée efficacement par de la vitamine B6

Author: M. Haas, M. Le Gall-Godard, Cedric Pastoret, Patrick Jego, N. Belhomme, B. Henriot, J.-S. Allain, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 2. Zero hunger, Gynecology, medicine.medical_specialty, business.industry, Treatment outcome, Gastroenterology, Anémie sidéroblastique, [SDV.CAN]Life Sciences [q-bio]/Cancer, Alcoolisme, Carence en vitamine B6, 3. Good health, 03 medical and health sciences, Carence en acide folique, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal Medicine, medicine, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: Resume Introduction L’anemie sideroblastique est une cause rare d’anemie microcytaire, caracterisee par la presence de sideroblastes en couronne au myelogramme. Cette anemie peut etre congenitale ou bien acquise, due a une myelodysplasie ou favorisee par des carences, des medicaments et des toxiques. Observation Nous rapportons le cas d’un homme alcoolique de 49 ans presentant une anemie microcytaire sideroblastique severe reliee a une carence en pyridoxine (vitamine B6). Il a aussi ete identifie une carence en folates. L’hemogramme s’est corrige en un mois avec une supplementation vitaminique. Conclusion Chez les sujets a risque, une carence en pyridoxine doit etre evoquee devant une anemie sideroblastique.
Published: 2019
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166. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study

Author: Daniel Delgadillo, Carole Soussain, Bachir Aidaoui, Eileen M Boyle, Philippe Agapé, Vincent Delwail, Agusti Alentorn, Adrien Chauchet, Olivier Casasnovas, Hassen Douzane, Franck Morschhauser, Magali Le Garff-Tavernier, Marie Blonski, Olivier Chinot, Luc Taillandier, Matthieu Peyre, Myrto Costopoulos, Chantal Campello, Fabrice Jardin, Jerome Tamburini, Aurélie Kas, Alexandra Amiel, Frédéric Charlotte, Michel Fabbro, Karima Mokhtari, Emeline Tabouret, Caroline Houillier, Valérie Touitou, Agathe Waultier, Jacques-Olivier Bay, Gandhi Damaj, Nadine Martin-Duverneuil, Lucie Oberic, Julie Abraham, Roch Houot, Hervé Ghesquières, Marie-Pierre Moles-Moreau, Remy Gressin, Corinne Haioun, Adrian Tempescul, Diane Genet, Thierry Lamy, Safia Chebrek, Philippe Colin, Anna Schmitt, Sylvain Choquet, Cécile Moluçon-Chabrot, Jean-Pierre Marolleau, Guido Ahle, Loïc Feuvret, Luc-Matthieu Fornecker, Khê Hoang-Xuan, Emmanuel Gyan, Kamel Laribi, Bertrand Mathon, Caroline Serrier, Pierre Soubeyran, Nathalie Cassoux, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de neurophysiopathologie (INP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, medicine.medical_specialty, Antimetabolites, Antineoplastic, Palliative care, Adolescent, Databases, Factual, Lymphoma, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Article, Central Nervous System Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, hemic and lymphatic diseases, Outcome Assessment, Health Care, medicine, Humans, Progression-free survival, Young adult, education, Aged, Retrospective Studies, education.field_of_study, business.industry, Age Factors, Retrospective cohort study, Middle Aged, Combined Modality Therapy, Progression-Free Survival, 3. Good health, Transplantation, Clinical trial, Methotrexate, 030220 oncology & carcinogenesis, Rituximab, Neurology (clinical), France, Cranial Irradiation, business, 030217 neurology & neurosurgery, medicine.drug, Stem Cell Transplantation
Abstract: ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients 60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.
Published: 2019
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167. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network

Author: Roch Houot, Khê Hoang-Xuan, Aline Clavert, Hervé Ghesquières, A. El Yamani, Eileen M Boyle, Marie Blonski, Sylvain Choquet, M. Ertault de la Bretonnière, Cécile Moluçon-Chabrot, Nathalie Cassoux, Valérie Touitou, Fontanet Bijou, Carole Soussain, S. Leruez, Maryline Barrie, E. Nicolas-Virelizier, S. Coisy, M.L. Lelez, M. Daniau, Caroline Houillier, Remy Gressin, D. Leclercq, Keyvan Rezai, Institut Curie [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Bergonié [Bordeaux], UNICANCER, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), European Molecular Biology Laboratory [Grenoble] (EMBL), Hôpital Lapeyronie [Montpellier] (CHU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Janssen BiotechPharmacyclicsJanssen Biotech, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Lymphoma, Phases of clinical research, Gene mutation, Central Nervous System Neoplasms, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, hemic and lymphatic diseases, Prospective Studies, Relapse, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Ibrutinib, Middle Aged, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Toxicity, Female, medicine.medical_specialty, Retinal Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Primary vitreoretinal lymphoma, 03 medical and health sciences, Refractory, Internal medicine, medicine, Humans, Aged, Salvage Therapy, business.industry, Adenine, Induction chemotherapy, medicine.disease, Clinical trial, 030104 developmental biology, Pyrimidines, chemistry, Primary CNS lymphoma, Drug Resistance, Neoplasm, Pyrazoles, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: Background Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL Patients and methods This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 30%). Results Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7–30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8–12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. Conclusion Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. Clinical trial number NCT02542514 .
Published: 2019
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168. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Author: Bertrand Joly, Hagay Sobol, Isabelle Azais, Hervé Avet-Loiseau, Karine Augeul-Meunier, Catherine Le Bris, Delphine Demangel, Maroulio Pertesi, Xavier Leleu, Maria Victoria Revuelta, Maxime Vallée, Manuel Cliquennois, James D. McKay, Aurore Perrot, Aleksandra Butrym, Matthieu Foll, Björn Nilsson, Javier Oliver, Judit Várkonyi, Emeline Perrial, Xiaomu Wei, Artur Jurczyszyn, Gabriele Buda, Marcin Rymko, Cécile Leyronnas, Robert J. Klein, Elżbieta Iskierka-Jażdżewska, Claire Mathiot, Marzena Wątek, Eric Voog, Olivier Decaux, Florence Desquesnes, Jill Corre, Arnon Nagler, Jean Gabriel Fuzibet, Véronique Dorvaux, Jan Maciej Zaucha, Philippe Rodon, Siwei Chen, Denis Caillot, Laurent Garderet, Michel Maigre, Isabelle Leduc, Fabienne Lesueur, Borhane Slama, Sophie Rigaudeau, Philippe Mineur, Norbert Grząśko, Perrine Galia, Rui Manuel Reis, Federico Canzian, Philippe Helias, Yves-Jean Bignon, Marcin Kruszewski, Victor Moreno, Juan Sainz, Nathalie Cheron, Laurent Voillat, Charles Dumontet, Christian Berthou, Marie Beaumont, Brigitte Pegourie, Etienne Paubelle, Marguerite Vignon, Matteo Pelosini, Philippe Casassus, Isabelle Lambrecht, Laure Vincent, Eileen M Boyle, Annette Juul Vangsted, Pascal Bourquard, Laurent Mosser, Margaret Macro, Gerald Marit, Daniele Campa, Brigitte Kolb, Bruno Royer, Jean Fontan, Ramón García-Sanz, Philippe Moreau, Serge Leyvraz, Malgorzata Krawczyk-Kulis, Krzysztof Jamroziak, Joaquin Martinez-Lopez, Bruno Anglaret, Steven M. Lipkin, Nicole Frenkiel, Ofure Obazee, Marek Dudziński, Pascale Cony-Makhoul, Hervé Naman, Andres Jerez, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Genetic Cancer Susceptibility, Department of Biological Statistics and Computational Biology, Cornell University, Weill Medical College of Cornell University Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University [New York], Hospices Civils de Lyon (HCL), ProfileXpert, Université de Lyon, LCMT, ProfileXpert, Biomedical Research Institute of Málaga (IBIMA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [APHP], Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, INSERM UMR S1146, Laboratoire d'Imagerie Biomédicale, France, parent, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Médecine Interne [CHU Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, Service d'Hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), Département Oncologie-Hématologie [Charleroi, Belgium], Grand Hôpital de Charleroi [Belgium], Centre Jean Bernard [Le Mans] (Institut Inter-Régional de Cancérologie), CHU de Fort de France (Service Post-Urgences, Pôle RASSUR), CHU de Fort de France, Hôpital JeanMinjoz, Centre hospitalier de Chartres (Chartres) (Service d'Hémato-Oncologie), Service hématologie (CHU d'Amiens), CHU Amiens-Picardie, Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [AP-HP Hôpital Saint-Louis], AP-HP Hôpital Saint-Louis, Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], CHU Saint Louis [APHP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Interne [CHU Nice] (Hôpital l'Archet), Hôpital l'Archet-Centre Hospitalier Universitaire de Nice (CHU de Nice), Service d'hématologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hematology Department - Namur Thrombosis and Hemostasis Center (NTHC), UCL Mont-Godinne, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHUV, Lausanne (Departement d'Oncologie), Unité d'Oncologie Médicale, Rodez (Hôpital Jacques Puel, Pôle Medical 2), Unité de coordination en oncogériatrie de Basse-Normandie [Caen] (UCOG Basse-Normandie), CHI Poissy-Saint-Germain, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CHG Abbeville (Hématologie), Institut Daniel Hollard [Grenoble], Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Intergroupe francophone du myélome (IFM), Service d'Onco-Hématologie, Centre Médical de Bligny, Briis sous Forges, Service Hématologie, CH LYON SUD, Pierre benite, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital Sud-Fancilien, CH Sud-Fancilien, Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU de Nîmes), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématologie, Oncologie Médicale, Centre Azureen de cancérologie, Centre Azureen de cancérologie, Unité d'hématologie et d'oncologie [Centre Hospitalier de Versailles], Centre Hospitalier de Versailles (CHV), Inserm U1035, Biotherapies des Maladies Genetiques et Cancers, Univ Bordeaux, CHU de Bordeaux, Pole de Biologie et Pathologie, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Rhumatologie [Reims], Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Hospitalier et Universitaire de Pointe-à-Pitre (Oncologie Médicale), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), Instituto de Salud Carlos III (ISC), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], Barretos Cancer Hospital [São Paulo, Brazil], Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary, Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Departement of Hematology, University Hospital, Bydgoszcz, Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Department of Hematology, Jagiellonian University - Medical College, Gdynia Oncology Center, Gdynia and Department of Oncological Propedeutics, Genomic Oncology Area (GENYO), Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Department of Hematology, Insitute of Hematology and Transfusion Medicine, Warsa, Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Department of Hematology, Medical University of Lodz, Departement of Experimental Hemato-Oncology, Medical University of Lubli (Polish Myeloma Study Group), Servicio de Hematología, Hospital Universitario 12 de Octubre [Madrid], Hematology and Medical Oncology Department, Hospital Morales Meseguer, Murcia (IMIB), Department of Biology, University of Pisa, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematology Department, Teaching Hospital No1, Rzeszow, Teaching Hospital N°1, Haematology Department, University Hospital of Salamanca, Hematology Division Chaim Sheba Medical Center, Tel Hashomer, Department of Hematology Copernicus Hospital, Torun, Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Wroclaw Medical University, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Agency for Cancer Research (IACR), INSERM 1052, CNRS 5286, CRCL Lyon, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UPS), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Charleroi (Hématologie et pathologies de la coagulation), Centre Hospitalier Universitaire de Charleroi, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie Génétique, de Prévention et Dépistage, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Département Universitaire Nice (Internal Medicine Department), Hôpital de Nice, Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13), Laboratoire de diagnostic génétique et moléculaire, Centre Jean Perrin, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Dijon, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Caen, Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de génomique du myélome [IUCT Oncopole, Toulouse], IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CIBER de Epidemiología y Salud Pública (CIBERESP), Biomarkers and Susceptibility Unit, Catalan Institute of Oncology, Molecular Oncology Research Center [São Paulo, Brazil], Centro de Genomica e Investigacion Oncologica (GENYO), Hospital universitario 12 de Octubre, Holycross Cancer Center of Kielce, Hematology Clinic, Department of Laboratory Medicine Lunds University Hospital Lund, Cornell University [New York], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Laboratoire d'Hématologie [CHU Amiens], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier de Versailles André Mignot (CHV), Instituto de Salud Carlos III [Madrid] (ISC), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Lund University [Lund], Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université catholique de Lille (UCL), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Pisa - Università di Pisa, Mines Paris - PSL (École nationale supérieure des mines de Paris), Wrocław Medical University, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté de Médecine (UR Médecine), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, Letter, [SDV]Life Sciences [q-bio], MEDLINE, Library science, Myeloma, World health, 03 medical and health sciences, 0302 clinical medicine, Multiple myeloma, immune system diseases, Political science, hemic and lymphatic diseases, Exome Sequencing, Genetics, Humans, Exome, Genetic Predisposition to Disease, Cancer genetics, Exome sequencing, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, Exosome Multienzyme Ribonuclease Complex, Extramural, Mieloma múltiple, French, Hematology, language.human_language, 3. Good health, Pedigree, [SDV] Life Sciences [q-bio], Exome/genetics, Exosome Multienzyme Ribonuclease Complex/genetics, Female, Genetic Predisposition to Disease/genetics, Germ-Line Mutation/genetics, Multiple Myeloma/genetics, Whole Exome Sequencing/methods, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Donation, language, Multiple Myeloma, Genètica, International agency
Abstract: French National Cancer Institute (INCA) and the Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myelome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myelome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization
Published: 2019
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169. Combination lenalidomide-rituximab immunotherapy activates anti-tumour immunity and induces tumour cell death by complementary mechanisms of action in follicular lymphoma

Author: Marie-Hélène Delfau-Larue, Anita Gandhi, Preeti Trisal, Despoina Papazoglou, Asma Beldi-Ferchiou, Carla Guarinos, Karin Tarte, Patrick Hagner, Franck Morschhauser, Alan G. Ramsay, Soraya Carrancio, Chad C. Bjorklund, Hsiling Chiu, Estela G. Toraño, Celgene Corporation, School of Cancer and Pharmaceutical Sciences [London, UK] (Faculty of Life Sciences & Medicine), King‘s College London, Département d'immunobiologie et d'hématobiologie [CHU Henri Mondor], CHU Henri Mondor [Créteil], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Claude Huriez [Lille], CHU Lille, Celgene, CHU Henri Mondor, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, Université de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365, Hôpital Henri Mondor, Centre Hospitalier Universitaire [Rennes], AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA], Celgene Corporation [San Diego, CA, USA], Celgene Institute for Translational Research Europe [Seville, Spain], and Hôpital Claude Huriez
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Myeloid, Immunological Synapses, Neutrophils, medicine.medical_treatment, Follicular lymphoma, CD8-Positive T-Lymphocytes, Lymphocyte Activation, immunomodulation, antibody‐dependent cell‐mediated cytotoxicity, 0302 clinical medicine, Immunophenotyping, non-Hodgkin lymphoma, antibody-dependent cell-mediated cytotoxicity, lenalidomide, follicular lymphoma, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, Cytotoxic T cell, non‐Hodgkin lymphoma, Lymphoma, Follicular, Antibody-dependent cell-mediated cytotoxicity, B-Lymphocytes, Haematological Malignancy, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Vincristine, 030220 oncology & carcinogenesis, Cytokines, Rituximab, Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Research Paper, medicine.drug, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Lymphocyte Count, Cyclophosphamide, Cell Proliferation, Lenalidomide, business.industry, Antibody-Dependent Cell Cytotoxicity, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Doxorubicin, Drug Resistance, Neoplasm, Cancer research, Prednisone, business, 030215 immunology
Abstract: International audience; Chemotherapy plus rituximab has been the mainstay of treatment for follicular lymphoma (FL) for two decades but is associated with immunosuppression and relapse. In phase 2 studies, lenalidomide combined with rituximab (R 2 ) has shown clinical synergy in front-line and relapsed/refractory FL. Here, we show that lenalidomide reactivated dysfunctional T and Natural Killer (NK) cells ex vivo from FL patients by enhancing proliferative capacity and T-helper cell type 1 (Th1) cytokine release. In combination with rituximab, lenalidomide improved antibody-dependent cellular cytotoxicity in sensitive and chemo-resistant FL cells, via a cereblon-dependent mechanism. While single-agent lenalidomide and rituximab increased formation of lytic NK cell immunological synapses with primary FL tumour cells, the combination was superior and correlated with enhanced cytotoxicity. Immunophenotyping of FL patient samples from a phase 3 trial revealed that R 2 treatment increased circulating T- and NK-cell counts, while R-chemotherapy was associated with reduced cell numbers. Finally, using an in vitro model of myeloid differentiation, we demonstrated that lenalidomide caused a reversible arrest in neutrophil maturation that was distinct from a cytotoxic chemotherapeutic agent, which may help explain the lower rates of neutropenia observed with R 2 versus R-chemotherapy. Taken together, we believe these data support a paradigm shift in the treatment of FL – moving from combination immunochemotherapy to chemotherapy-free immunotherapy. © 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley and Sons Ltd.
Published: 2019
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170. Risk Factors for Postoperative Complications After Abdominal Panniculectomy and the Contribution of Plastic Surgeons on Reconstruction Following Massive Weight Loss

Author: Damien Bergeat, Eric Watier, Isabelle Pluvy, Camille Mocquard, Nicolas Bertheuil, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Weight loss, Risk Factors, Weight Loss, medicine, Humans, 030223 otorhinolaryngology, ComputingMilieux_MISCELLANEOUS, Surgeons, Nutrition and Dietetics, Abdominoplasty, business.industry, 3. Good health, Surgery, Abdominal Panniculectomy, Obesity, Morbid, 030220 oncology & carcinogenesis, medicine.symptom, business
Abstract: International audience; [No abstract available]
Published: 2019
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171. Impact of B cell/lymphoid stromal cell crosstalk in B-cell physiology and malignancy

Author: Karin Tarte, Claire Lamaison, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Région Bretagne, Fondation ARC pour la Recherche sur le Cancer PGA1 RF20170205386, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Stromal cell, Immunology, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Communication, Biology, Lymphocyte Activation, Somatic evolution in cancer, Cell plasticity, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cell Plasticity, Tumor Microenvironment, medicine, Animals, Humans, Immunology and Allergy, Lymphoma, Follicular, B cell, ComputingMilieux_MISCELLANEOUS, Cancer-associated fibroblasts, Cell Proliferation, B-Lymphocytes, Follicular dendritic cells, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Tumor niche, Fibroblastic reticular cells, Cancer research, Cancer-Associated Fibroblasts, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lymph Nodes, Stromal Cells, 030215 immunology
Abstract: Stromal cells have been considered for a long time essentially as a structural component organizing tissue architecture, including those of secondary lymphoid organs. More recently, highly specialized stromal cell subsets were shown to differentially organize immune cell recruitment, survival, and differentiation within lymph nodes. In particular, mature B cells interact with different lymphoid stromal cell networks through bidirectional interactions involving cell-cell contact and soluble factors. Follicular lymphoma (FL) is the paradigm of a B-cell malignancy dependent on a lymphoid-like microenvironment supporting tumor cell growth, drug resistance, and clonal evolution. This review provides an overview of our current knowledge of lymphoid stromal cell heterogeneity and functions in normal B-cell activation. In addition, we also depict the dynamic and plasticity of FL cancer-associated fibroblasts, the mechanisms underlying their key role within FL permissive niches, and their potential as therapeutic targets in this still fatal malignancy.
Published: 2019
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172. Mesenchymal stromal cells for systemic sclerosis treatment

Author: Pauline Lansiaux, Dominique Farge, Karin Tarte, Séverine Loisel, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), McGill University = Université McGill [Montréal, Canada], CHU Pontchaillou [Rennes], Etablissement Français du Sang Bretagne, EFS, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was supported by the the \'Fonds de Dotation de l'AFER pour la Recherche Médicale\', Paris, France [Grant call 2019], the \'Agence de Biomédecine\', Saint-Denis la Plaine, France [grant number 18GREFFE009, 2018], and the \'Cordons de Vie\' Association, Monaco [Grant call 2019]., Université Paris Cité (UPCité), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, Pathology, medicine.medical_specialty, medicine.medical_treatment, Immune modulation, Immunology, Mesenchymal stromal cells, Adipose tissue, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mesenchymal Stem Cell Transplantation, 03 medical and health sciences, Clinical trials, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, Fibrosis, Animals, Humans, Immunology and Allergy, Medicine, skin and connective tissue diseases, Skin, 030203 arthritis & rheumatology, Autoimmune disease, Scleroderma, Systemic, integumentary system, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Stem-cell therapy, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Systemic sclerosis, Angiogenesis, Bone marrow, business
Abstract: International audience; Systemic sclerosis (SSc) is a rare chronic autoimmune disease characterized by vasculopathy, dysregulation of innate and adaptive immune responses, and progressive fibrosis. SSc remains an orphan disease, with high morbity and mortality in SSc patients. The mesenchymal stromal cells (MSC) demonstrate in vitro and in vivo pro-angiogenic, immuno-suppressive, and anti-fibrotic properties and appear as a promising stem cell therapy type, that may target the key pathological features of SSc disease. This review aims to summarize acquired knowledge in the field of :1) MSC definition and in vitro and in vivo functional properties, which vary according to the donor type (allogeneic or autologous), the tissue sources (bone marrow, adipose tissue or umbilical cord) or inflammatory micro-environment in the recipient; 2) preclinical studies in various SSc animal models , which showed reduction in skin and lung fibrosis after MSC infusion; 3) first clinical trials in human, with safety and early efficacy results reported in SSc patients or currently tested in several ongoing clinical trials.
Published: 2021
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173. Soluble programmed death-ligand 1 as a prognostic biomarker for overall survival in patients with diffuse large B-cell lymphoma: a replication study and combined analysis of 508 patients

Author: Karin Tarte, Thomas E. Witzig, Imane Azzaoui, Thomas M. Habermann, Andrew L. Feldman, Céline Pangault, Noel Milpied, Stephen M. Ansell, Thierry Fest, Marie Parrens, Matthew J. Maurer, James R. Cerhan, Delphine Rossille, Mikael Roussel, Susan L. Slager, Thierry Lamy, Gaëlle Labouré, Brian K. Link, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Mayo Clinic [Rochester], CHU Bordeaux [Bordeaux], University of Iowa [Iowa City], This study is supported by the French Health Minister (BMS_LyTrans project, NCT01287923), the National Institute of Cancer (INCa Translational Research 2010), the French Lymphoma Study Association (LYSA), the French National Agency for Research (ANR Carnot/CALYM), the National Cancer Institute (P50 CA97274, R01 CA92153), and the Henry J Predolin Foundation. Concerning the French cohort, we are indebted to the LYSA pathology platform (Hôpital Henri Mondor, Créteil) for immunohistochemical experiments, the Centre de Ressources Biologiques CRB-Santé (BB-0033-00056) of the Rennes hospital for providing high quality samples. This work was partly supported by a French National Cancer Institute post-doctoral fellowship (grant number PDOC-RC-GO/07-003) to the first author (D.R.)., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Chard-Hutchinson, Xavier
Subjects: Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, medicine.medical_specialty, Adolescent, Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Refractory, immune system diseases, hemic and lymphatic diseases, Internal medicine, Biomarkers, Tumor, Tumor Microenvironment, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Hematology, business.industry, Peripheral tolerance, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Prognosis, medicine.disease, 3. Good health, Lymphoma, Leukemia, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Immunology, Cancer research, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug
Abstract: Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematologic malignancy with more than two-thirds of the patients cured with first-line rituximab-based treatments. However, relapsing or refractory patients have a very poor survival despite salvage therapies. The PD-1/PD-L1 pathway plays a major role in peripheral tolerance and homeostasis by inhibiting T-cell activation.
Published: 2017
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174. Potential drug-drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay

Author: Thierry Lamy, Lydia Sanchez, Astrid Bacle, Pascal Le Corre, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes 1 - Faculté des sciences pharmaceutiques et biologiques (UR1 Pharmacie), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes - Faculté des sciences pharmaceutiques et biologiques (UR Pharmacie), Université de Rennes (UR), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Drug, Drug–drug interactions, Cancer Research, Vincristine, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, media_common.quotation_subject, Renal function, Pharmacokinetic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Toxicology, Kidney, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Internal medicine, Medicine, Humans, Pharmacology (medical), Drug Interactions, Bone marrow transplantation unit stay, Nephrotoxicity, media_common, Retrospective Studies, Pharmacology, Chemotherapy, Pharmacodynamic, business.industry, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Length of Stay, Middle Aged, 3. Good health, Intensive Care Units, 030104 developmental biology, Oncology, Pharmaceutical Preparations, 030220 oncology & carcinogenesis, Pharmacodynamics, Hematologic Neoplasms, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Methotrexate, Hematopoietic stem cell transplant, business, medicine.drug, Glomerular Filtration Rate
Abstract: International audience; Purpose - Studies have documented potential drug-drug interactions (pDDIs) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents, and supportive-care drugs, studies on potential DDIs are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDIs, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay. Methods - Retrospective study in 31 adult patients consecutively admitted to the BMTU. Results - Prevalence of pharmacokinetic interactions was ten times lower than the pharmacodynamic interactions. The contraindications were rare, and only of pharmacokinetic origin. The main drugs involved in pharmacokinetic DDIs were ciclosporine, methotrexate, esomeprazole, tramadol, and vincristine. The median number of potential nephrotoxicity-related DDIs per patient was 7 and the median number of days during which nephrotoxicity-related DDIs potentially occurred was 77 days per patient. The decrease in glomerular filtration rate (GFR) throughout the BMTU stay (mean decrease of 13 ml/min) was correlated with the number of days of potential nephrotoxic drug interactions. Conclusions - Potential DDIs in HCST patients in BMTU were quite common. The DDIs from pharmacokinetic origin were less frequent, but of higher grade, than those of pharmacodynamic origin. The decrease in GFR suggests that the density of potential nephrotoxic drug interactions may be an issue to be considered in these patients.
Published: 2019
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175. Adipose mesenchymal stromal cells Definition, immunomodulatory properties, mechanical isolation and interest for plastic surgery

Author: Benoit Chaput, Eric Watier, Cédric Ménard, Audrey Varin, Karin Tarte, Jérôme Laloze, Nicolas Bertheuil, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, Adipose stromal cells, Nanofat grafting, Adipose tissue, Tissu adipeux, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030230 surgery, Mesenchymal Stem Cell Transplantation, Regenerative Medicine, Regenerative medicine, Immunomodulation, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Fat grafting, Humans, Medicine, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, Immunomodulatory properties, Stromal vascular fraction, Clinical routine, Adipose stem cells, 3. Good health, Plastic surgery, Adipose Tissue, Cellules souches, Cancer research, Surgery, business, Cellules stromales mésenchymateuses du tissu adipeux
Abstract: International audience; Ever since their discovery in 2001, adipose mesenchymal stromal cells (ASC) have profoundly modified clinical indications and our practice of plastic surgery, thereby placing our discipline at the forefront of regenerative medicine. These cells act through paracrine signaling by synthesizing immunosuppressive and pro-angiogenic factors. They are of key importance with regard to the regenerative properties of autologously grafted adipose tissue (AT). Taken together, they make up the stromal vascular fraction (SVF) comprising all AT cells except for adipocytes. As our knowledge evolves, we are moving from fat grafting towards SVF grafting, of which the essential sought-after effect is tissue regeneration. The objective of the present review is to synthesize present-day information on ASCs and their immunomodulatory properties and, from a practical standpoint, to indicate present-day and future steps towards establishment of clinical routine, particularly through application of techniques favoring mechanical digestion of adipose tissue.
Published: 2019
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176. [Retracted] 3'RR and 5'E immunoglobulin heavy chain enhancers are independent engines of locus remodeling

Author: Hussein Issaoui, François Boyer, Yves Denizot, Alexis Saintamand, Ophélie Alyssa Martin, Nour Ghazzaui, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent
Subjects: Genetics, 0303 health sciences, IgH 3′ regulatory region, [SDV.IMM] Life Sciences [q-bio]/Immunology, Eμ, Immunology, Locus (genetics), Biology, 3. Good health, RAG-deficient mice, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Knockout mouse, Immunology and Allergy, Immunoglobulin heavy chain, [SDV.IMM]Life Sciences [q-bio]/Immunology, Enhancer, Transcriptional enhancer, knockout mice, 030304 developmental biology, 030215 immunology
Abstract: The authors have retracted this Correspondence. After the publication of this correspondence, it came to the authors’ attention that the control RAG2−/− mouse was a RAG2−/−γc−/− mouse. This point resulted in the conclusions being considered invalid. The authors apologize to the journal and its readers for any inconvenience caused. https://doi.org/10.1038/s41423-021-00715-7; International audience; The authors have retracted this Correspondence. After the publication of this correspondence, it came to the authors’ attention that the control RAG2−/− mouse was a RAG2−/−γc−/− mouse. This point resulted in the conclusions being considered invalid. The authors apologize to the journal and its readers for any inconvenience caused. https://doi.org/10.1038/s41423-021-00715-7
Published: 2019
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177. Deletion of the immunoglobulin heavy chain 3' regulatory region super-enhancer affects somatic hypermutation in B1 B cells

Author: Saintamand Alexis, Boyer François, Denizot Yves, Issaoui Hussein, Ghazzaui Nour, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and ANR-16-CE12-0017,EpiSwitch-3RR,Dissection génétique et fonctionnelle du rôle de la région de contrôle du locus IgH au cours de la commutation isotypique(2016)
Subjects: Immunology, Somatic hypermutation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Regulatory Sequences, Nucleic Acid, Biology, Regulatory region, Mice, 03 medical and health sciences, 0302 clinical medicine, Super-enhancer, Cytidine Deaminase, Correspondence, Animals, Immunology and Allergy, 3' Flanking Region, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Sequence Deletion, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, 3. Good health, Cell biology, Enhancer Elements, Genetic, Infectious Diseases, 030220 oncology & carcinogenesis, Immunoglobulin heavy chain, Somatic Hypermutation, Immunoglobulin, Immunoglobulin Heavy Chains
Abstract: International audience
Published: 2019
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178. The Cassini VIMS archive of Titan: From browse products to global infrared color maps

Author: Jason W. Barnes, S. Le Mouélic, Jason M. Soderblom, Benoît Seignovert, Sebastien Rodriguez, Roger N. Clark, Philip D. Nicholson, Robert H. Brown, Thomas Cornet, B. J. Buratti, Jérémie Lasue, V. Pasek, Kevin H. Baines, Christophe Sotin, Laboratoire de Planétologie et Géodynamique [UMR 6112] (LPG), Université d'Angers (UA)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Formation et de Recherche sur les Environnements Méditérranéens (CEFREM), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Moscow,USA], University of Idaho [Moscow, USA], Lunar and Planetary Laboratory [Tucson] (LPL), University of Arizona, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), California Institute of Technology (CALTECH), Department of Astronomy [Ithaca], Cornell University [New York], Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Massachusetts Institute of Technology (MIT), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire SITI [CHU Rennes], Etablissement français du sang [Rennes] (EFS Bretagne)-CHU Pontchaillou [Rennes], Université de Perpignan Via Domitia (UPVD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Bern- University of Bern [Bern], Partenaires INRAE, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), DLR Institute of Planetary Research, German Aerospace Center (DLR), US Geological Survey [Denver], United States Geological Survey [Reston] (USGS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Brightness, Haze, 010504 meteorology & atmospheric sciences, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Multispectral image, FOS: Physical sciences, 01 natural sciences, law.invention, law, 0103 physical sciences, Radiative transfer, Imaging science, Radar, 010303 astronomy & astrophysics, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Remote sensing, Earth and Planetary Astrophysics (astro-ph.EP), Spectrometer, Pixel, Astronomy and Astrophysics, 13. Climate action, Space and Planetary Science, [SDU]Sciences of the Universe [physics], Geology, Astrophysics - Earth and Planetary Astrophysics
Abstract: International audience; We have analyzed the complete Visual and Infrared Mapping Spectrometer (VIMS) data archive of Titan. Our objective is to build global surface cartographic products, by combining all the data gathered during the 127 targeted flybys of Titan into synthetic global maps interpolated on a grid at 32 pixels per degree (∼1.4 km/pixel at the equator), in seven infrared spectral atmospheric windows. Multispectral summary images have been computed for each single VIMS cube in order to rapidly identify their scientific content and assess their quality. These summary images are made available to the community on a public website (vims.univ-nantes.fr). The global mapping work faced several challenges due to the strong absorbing and scattering effects of the atmosphere coupled to the changing observing conditions linked to the orbital tour of the Cassini mission. We determined a surface photometric function which accounts for variations in incidence, emergence and phase angles, and which is able to mitigate brightness variations linked to the viewing geometry of the flybys. The atmospheric contribution has been reduced using the subtraction of the methane absorption band wings, considered as proxies for atmospheric haze scattering. We present a new global three color composite map of band ratios (red: 1.59/1.27 µm; green: 2.03/1.27 µm; blue: 1.27/1.08 µm), which has also been empirically corrected from an airmass (the solar photon path length through the atmosphere) dependence. This map provides a detailed global color view of Titan's surface partially corrected from the atmosphere and gives a global insight of the spectral variability, with the equatorial dunes fields appearing in brownish tones, and several occurrences of bluish tones localized in areas such as Sinlap, Menvra and Selk craters. This kind of spectral map can serve as a basis for further regional studies and comparisons with radiative transfer outputs, such as surface albedos, and other additional data sets acquired by the Cassini Radar (RADAR) and Imaging Science Subsystem (ISS) instruments.
Published: 2019
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179. The Assessment of a Predictive Risk and a Decrease Postoperative Complication Following Body-Contouring Surgery After Massive Weight Loss

Author: Nathalie Kerfant, Damien Bergeat, Nicolas Bertheuil, Camille Mocquard, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: medicine.medical_specialty, Nutrition and Dietetics, business.industry, Endocrinology, Diabetes and Metabolism, Postoperative complication, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030230 surgery, Body contouring surgery, Surgery, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Weight loss, medicine, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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180. Pan-HDAC Inhibitors Restore PRDM1 Response to IL21 in CREBBP-Mutated Follicular Lymphoma

Author: Marc-Antoine Belaud-Rotureau, Eric Guiheneuf, Thierry Lamy, Jerome Le Priol, Fabrice Jardin, Céline Pangault, Gersende Caron, Catherine Henry, Mikael Roussel, Valérie Camara-Clayette, Francisco Llamas-Gutierrez, Thierry Fest, Pascal Godmer, Fabienne Desmots, Vincent Ribrag, Karin Tarte, Cedric Pastoret, Etablissement français du sang [Rennes] (EFS Bretagne), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), BB-0033-00056, Citrus Research Board, Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, STAT3 Transcription Factor, Cancer Research, Plasma Cells, Follicular lymphoma, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Plasma cell, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, PRDM1, Follicular phase, Plasma cell differentiation, medicine, Humans, Lymphoma, Follicular, Gene Expression Profiling, Interleukins, Germinal center, medicine.disease, BCL6, Germinal Center, CREB-Binding Protein, Lymphoma, Gene Expression Regulation, Neoplastic, Histone Deacetylase Inhibitors, 030104 developmental biology, medicine.anatomical_structure, Oncology, Mutation, Cancer research, Proto-Oncogene Proteins c-bcl-6, Positive Regulatory Domain I-Binding Factor 1, Neoplasm Grading, Transcriptome, 030215 immunology, Protein Binding
Abstract: Purpose: Follicular lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of follicular lymphoma cells and loss-of-function of CREBBP acetyltransferase. Experimental Design: The study used human primary cells obtained from either follicular lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches. Results: Conversely to normal B cells, follicular lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the follicular lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In follicular lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these follicular lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with follicular lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of follicular lymphoma B cells in the differentiation process. Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with follicular lymphoma through the induction of the expression of plasma cell genes.
Published: 2019
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181. High-throughput sequencing reveals similar molecular signatures for class switch recombination junctions for the γ and α isotypes

Author: Hussein Issaoui, Yves Denizot, Alexis Saintamand, Nour Ghazzaui, François Boyer, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and ANR-16-CE12-0017,EpiSwitch-3RR,Dissection génétique et fonctionnelle du rôle de la région de contrôle du locus IgH au cours de la commutation isotypique(2016)
Subjects: Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, DNA sequencing, Mice, 03 medical and health sciences, 0302 clinical medicine, Text mining, [SDV.CAN] Life Sciences [q-bio]/Cancer, Correspondence, Animals, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Recombination, Genetic, Physics, B-Lymphocytes, 0303 health sciences, business.industry, High-Throughput Nucleotide Sequencing, Immunoglobulin Class Switching, Immunoglobulin Isotypes, Infectious Diseases, Immunoglobulin class switching, business, 030215 immunology
Abstract: International audience
Published: 2019
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182. The Lipo-Body Lift Operative Technique

Author: Camille Mocquard, Damien Bergeat, Benoit Chaput, Nicolas Bertheuil, Christophe Morvan, Eric Watier, Jonchère, Laurent, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: Contouring, medicine.medical_specialty, Lift (data mining), business.industry, Gold standard, lcsh:Surgery, Video, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RD1-811, 030230 surgery, Surgery, 03 medical and health sciences, 0302 clinical medicine, Lower body, [SDV.CAN] Life Sciences [q-bio]/Cancer, Weight loss, 030220 oncology & carcinogenesis, medicine, Postoperative results, medicine.symptom, business, Lower trunk
Abstract: International audience; Bariatric surgery induces massive weight loss, which results in global and complex skin deformities. Lower body lift procedure has become the gold standard for lower trunk reconstruction. The authors describe in this video the lipo-body lift technique in detail. The video is divided into 4 parts part 1, indications and preoperative markings; part 2, posterior contouring; part 3, anterior contouring; and part 4, preoperative and postoperative results. Patient selection and technical key points of the technique are discussed. The lipo-body lift method is an important component of reconstructive strategies and should be widely offered to patients who experienced massive weight loss.
Published: 2019
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183. How to make usage of the standardized EuroFlow 8-color protocols possible for instruments of different manufacturers

Author: Sebastian Böttcher, Margarida Lima, Alberto Orfao, Ana Helena Santos, Ester Mejstříková, Hana Glier, Tomasz Szczepański, Naděžda Brdičková, Juan Flores-Montero, Paula Fernández, Tomas Kalina, Jacques J.M. van Dongen, Michaela Novakova, Marcela Vlková, Vincent H.J. van der Velden, Bruno Paiva, Leire Burgos, Mikael Roussel, Immunology, Ministry of Health of the Czech Republic, Ministry of Education, Youth and Sports (Czech Republic), European Commission, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Childhood Leukaemia Investigation Prague (CLIP), University Hospital Motol [Prague], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Rostock, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Clínica Universidad de Navarra [Pamplona], Leiden University Medical Center (LUMC), 15-28525A, Ministerstvo Zdravotnictví Ceské Republiky, Ministerio de Economía y Competitividad, Ministry of Education, Youth and Sports, Czech Republic, CZ.2.16/3.1.00/24505, European Structural funds, 802214, GAUK, CB16/12/00400, Instituto de Salud Carlos II, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Universiteit Leiden
Subjects: 0301 basic medicine, Standardization, Computer science, EuroFlow, Immunology, Nanotechnology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorescent spectrum, Fluorochromes, Immunophenotyping, 03 medical and health sciences, Humans, Immunology and Allergy, Flow cytometry, Protocol (science), business.industry, Dynamic range, Scale (chemistry), 030104 developmental biology, Type iib, Filter (video), Hematologic Neoplasms, business, Computer hardware
Abstract: A critical component of the EuroFlow standardization of leukemia/lymphoma immunophenotyping is instrument setup. Initially, the EuroFlow consortium developed a step-by-step standard operating protocol for instrument setup of ≥ 8-color flow cytometers that were available in 2006, when the EuroFlow activities started. Currently, there are 14 instruments from 9 manufacturers capable of 3-laser excitation and ≥ 8 color measurements. The specific adaptations required in the instrument set-up to enable them to acquire the standardized 8-color EuroFlow protocols are described here. Overall, all 14 instruments can be fitted with similar violet, blue and red lasers for simultaneous measurements of ≥ 8 fluorescent dyes. Since individual instruments differ both on their dynamic range (scale) and emission filters, it is not accurate to simply recalculate the target values to different scale, but adjustment of PMT voltages to a given emission filter and fluorochrome, is essential. For this purpose, EuroFlow has developed an approach using Type IIB (spectrally matching) particles to set-up standardized and fully comparable fluorescence measurements, in instruments from different manufacturers, as demonstrated here for the FACSCanto II, and Navios and MACSQuant flow cytometers. Data acquired after such adjustment on any of the tested cytometry platforms could be fully superimposed and therefore analyzed together. The proposed approach can be used to derive target values for any combination of spectrally distinct fluorochromes and any distinct emission filter of any new flow cytometry platform, which enables the measurement of the 8-color EuroFlow panels in a standardized way, by creating superimposable datafiles., This work is the main output of grant 15-28525A from Ministry of Health of the Czech Republic (T.K.). Instruments and infrastructure were supported by Ministry of Education, Youth and Sports, Czech Republic NPU I no. LO1604 (T.K.). Sony SP6800 instrument was funded by European Structural fundsCZ.2.16/3.1.00/24505 (T.K.). M.N. was supported by GAUK802214. A.O. and J.F-M. were supported by grant DTS15/00119 and CB16/12/00400 from the Instituto de Salud Carlos II, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER.
Published: 2019
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184. Exploring T cell - B cell collaboration in multiple sclerosis through B cell differentiation analysis

Author: Morille, J., Rodriguez, S., Thomas, P. Ame, Karin Tarte, Garcia, A., Berthelot, L., Nicot, A., Brouard, S., Laplaud, D. A., Michel, L., Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

185. Low Frequency of Circulating T Follicular Helper 1 Cells Is Associated to Adequate Response to Adalimumab Therapy in Rheumatoid Arthritis

Author: Lucas, Charlotte, Codo, Roussine, Albert, Jean-David, Jean, Rachel, Rodriguez, Stéphane, Ame-Thomas, Patricia, Perdriger, Aleth, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

186. Mycobacterium tuberculosis prosthetic joint infections a case series and literature review

Author: Groupe d’Epidémiologie et Recherche en Infectiologie Clinique Centre-Ouest, Rozenn Le Berre, Yves Poinsignon, Olivier Grossi, Gregory Corvaisier, Guillaume Béraud, Cédric Arvieux, Nicolas Varache, Catherine Chirouze, Pierre Tattevin, Fabrice Uhel, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CH Bretagne Atlantique, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Nouvelles Cliniques Nantaises, Centre Hospitalier Le Mans (CH Le Mans), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service des maladies infectieuses et réanimation médicale, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Hôpital Jean Minjoz, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pontchaillou [Rennes], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), and Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes]
Subjects: Male, 0301 basic medicine, Arthroplasty, Replacement, Hip, medicine.medical_treatment, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, Medicine, 030212 general & internal medicine, Favorable outcome, Arthroplasty, Replacement, Knee, Surgical treatment, ComputingMilieux_MISCELLANEOUS, health care economics and organizations, Aged, 80 and over, biology, Disease Management, Middle Aged, Anti-Bacterial Agents, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Arthroplasty, Replacement, Shoulder, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, debridement, Microbiology (medical), medicine.medical_specialty, Prosthesis-Related Infections, Tuberculosis, Prosthetic joint, 030106 microbiology, education, Resection, Mycobacterium tuberculosis, 03 medical and health sciences, antituberculosis drug, Resection arthroplasty, Humans, Aged, Retrospective Studies, business.industry, medicine.disease, biology.organism_classification, Arthroplasty, Surgery, arthroplasty, Joints, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives - We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI).Methods - Cases of M. tuberculosis PJI documented in 7 referral French centers were retrospectively reviewed. Data were collected from medical files on a standardized questionnaire. We performed a literature review using the keywords 'prosthetic joint', and 'tuberculosis'. Results - During years 1997-2016, 13 patients (8 males, 5 females, median age 79 years [range, 60-86]) had documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to diagnosis was 9 years [0.4-20]. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months [6-32]). Nine patients underwent surgery: debridement (n = 4), resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. Seventeen additional cases of documented M. tuberculosis PJI have been reported, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement, 86% (19/22) with revision arthroplasty, and 81% (17/21) with resection (NS). Conclusions - M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment.
Published: 2019
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187. Cyclin D1-positive Mediastinal Large B-Cell Lymphoma With Copy Number Gains of CCND1 Gene

Author: Desmots, Fabienne, Roussel, Mikaël, Pangault, Céline, Llamas-Gutierrez, Francisco, Pastoret, Cedric, Guiheneuf, Eric, Le Priol, Jérôme, Camara-Clayette, Valérie, Caron, Gersende, Henry, Catherine, Belaud-Rotureau, Marc-Antoine, Godmer, Pascal, Lamy, Thierry, Tarte, Karin, Ribrag, Vincent, Fest, Thierry, Chen, Bo-Jung, Ruminy, Philippe, Roth, Christine, Bisig, Bettina, Mankel, Barbara, Steinhilber, Julia, Bohers, Elodie, Jardin, Fabrice, Fend, Falko, Swerdlow, Steven, Copie-Bergman, Christiane, De Leval, Laurence, Quintanilla-Martinez, Leticia, Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microenvironnement et cancer (MiCa), Service d'hématologie clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Etablissement français du sang [Rennes] (EFS Bretagne), Institut Gustave Roussy (IGR), Service de Cytogénétique et de Biologie Cellulaire, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier de Bretagne Atlantique, Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Centre Hospitalier Universitaire Sart Tilman, University of Tübingen, Institute of Pathology, Eberhard Karls Universität Tübingen, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pathology, and CHU Sart-Tilman
Subjects: [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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188. SMILE: a predictive model for scoring the severity of relapses in multIple sclerosis

Author: F. Le Frere, Anne Kerbrat, Yohann Foucher, Arthur Chatton, L. Michel, David-Axel Laplaud, E. Le Page, David Veillard, F. Lejeune, Sandrine Wiertlewski, Gilles Edan, Natacha Jousset, Stéphanie Hamonic, Jean-Christophe Ouallet, Bruno Brochet, Aurélie Ruet, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, medicine.medical_specialty, Multiple Sclerosis, Ataxia, Neurology, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Logistic regression, Disability Evaluation, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Lasso (statistics), Recurrence, Internal medicine, Relapse phenotype, Humans, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Therapeutic strategy, Neuroradiology, business.industry, Multiple sclerosis, medicine.disease, 3. Good health, Predictive model, Relapse recovery, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, EDSS, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), relapse severity and residual disability are difficult to predict. Nevertheless, this information is crucial both for guiding relapse treatment strategies and for informing patients. OBJECTIVE: We, therefore, developed and validated a clinical-based model for predicting the risk of residual disability at 6 months post-relapse in MS. METHODS: We used the data of 186 patients with RRMS collected during the COPOUSEP multicentre trial. The outcome was an increase of ≥ 1 EDSS point 6 months post-relapse treatment. We used logistic regression with LASSO penalization to construct the model, and bootstrap cross-validation to internally validate it. The model was externally validated with an independent retrospective French single-centre cohort of 175 patients. RESULTS: The predictive factors contained in the model were age > 40 years, shorter disease duration, EDSS increase ≥ 1.5 points at time of relapse, EDSS = 0 before relapse, proprioceptive ataxia, and absence of subjective sensory disorders. Discriminative accuracy was acceptable in both the internal (AUC 0.82, 95% CI [0.73, 0.91]) and external (AUC 0.71, 95% CI [0.62, 0.80]) validations. CONCLUSION: The predictive model we developed should prove useful for adapting therapeutic strategy of relapse and follow-up to individual patients.
Published: 2019
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189. Myeloid-Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets

Author: Elisabeth Ersvær, Helen A. Papadaki, Marie Lipoldová, Astrid Olsnes Kittang, Charalampos Pontikoglou, Suncica Bjelica, Slavko Mojsilović, Juan F. Santibanez, Nikoleta Bizymi, Mikael Roussel, Maria Velegraki, Jonchère, Laurent, University of Crete [Heraklion] (UOC), University of Belgrade [Belgrade], University of Bergen (UiB), Medical University of South Carolina [Charleston] (MUSC), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Western Norway University of Applied Sciences, Universidad Bernardo O'Higgins, Institute of Molecular Genetics [Prague, Czech Republic], Czech Academy of Sciences [Prague] (CAS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Angiogenesis, Inflammation, Review Article, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, medicine, Tumor Expansion, Hematology, lcsh:RC633-647.5, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Immune dysregulation, 3. Good health, Transplantation, 030220 oncology & carcinogenesis, Myeloid-derived Suppressor Cell, Cancer research, medicine.symptom, business, 030215 immunology
Abstract: International audience; Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.
Published: 2019
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190. Picturing Polarized Myeloid Phagocytes and Regulatory Cells by Mass Cytometry

Author: Jonathan M. Irish, Todd Bartkowiak, Mikael Roussel, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Vanderbilt University School of Medicine [Nashville], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent
Subjects: 0301 basic medicine, Myeloid, Phagocyte, Macrophage polarization, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Dendritic cells, Mass Spectrometry, Monocytes, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Macrophage, Humans, Mass cytometry, Myeloid regulatory cells, Phagocytes, Monocyte, Dendritic cell, Flow Cytometry, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Phenotype, Myeloid-derived suppressor cells, 030220 oncology & carcinogenesis, Myeloid-derived Suppressor Cell, Cytokines, Single-Cell Analysis
Abstract: International audience; The immune monocyte/phagocyte system (MPS) includes numerous cell subsets of the myeloid lineage including monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous both phenotypically and functionally. Previously, we characterized these diverse MPS phenotypes with multi-parametric mass cytometry (CyTOF). In order to expansively characterize monocytes, macrophages, and dendritic cells, a CyTOF panel was designed to measure 35 identity-, activation-, and polarization-markers. Here we provide a protocol to define a reference map for the myeloid compartment, including sample preparation, to produce reference cell subsets from the monocyte/phagocyte system. In particular, we focused on monocyte-derived macrophages that were further polarized in vitro with cytokine stimulation (i.e., M-CSF, GM-CSF, IL-4, IL-10, IFNγ, and LPS), as well as monocyte-derived DCs, and myeloid-derived suppressor cells (MDSCs), generated in vitro from human bone marrow and/or peripheral blood.
Published: 2019
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191. Biomarqueurs prédictifs de réponse aux inhibiteurs de points de contrôle immuns [Predictive biomarkers of response to immune checkpoint inhibitors.]

Author: Alexandra Lespagnol, Cédric Ménard, Romain Corre, Karin Tarte, Samuel Le Sourd, Jean Mosser, Marc Pracht, Julien Edeline, Alexandra Frelau, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CRLCC Eugène Marquis ( CRLCC ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'oncologie médicale, Molecular Engines Laboratories (MEL), Molecular Engines Laboratories, Microenvironnement et cancer (MiCa), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_treatment, Immunothérapie, [SDV.CAN]Life Sciences [q-bio]/Cancer, PD-L1 expression, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Biopsy, Medicine, Radiology, Nuclear Medicine and imaging, Neutrophil to lymphocyte ratio, ComputingMilieux_MISCELLANEOUS, Biomarqueurs, Anti-PD1, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, medicine.diagnostic_test, [ SDV ] Life Sciences [q-bio], business.industry, Hematology, General Medicine, Immunotherapy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Expression de PD-L1, Primary tumor, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Biomarker (medicine), Antibody, business, PD-1 blockades, Biomarkers
Abstract: International audience; Les anti-PD-1 s’imposent dernièrement comme un traitement de référence dans de nombreux cancers métastatiques. Ils présentent l’avantage d’une efficacité significative doublée d’un profil de toxicité favorable en monothérapie. Les taux et durées de réponse sont toutefois très variables, ce qui implique, vu leur coût, d’identifier des biomarqueurs prédictifs de réponse. Dans cette revue de la littérature, nous nous intéressons aux biomarqueurs de réponse des immunothérapies anti-PD1 et anti-CTLA-4. L’expression de PD-L1 par les cellules tumorales et du micro-environnement évaluée par immunohistochimie est prédictive de réponse pour certains cancers mais reste une approche mal standardisée avec différents anticorps, différents seuils de positivité et différentes cibles (tumeur ou micro-environnement). Il s’agit aussi d’une expression dynamique au cours du temps et hétérogène donc souvent discordante entre biopsies et pièces opératoires. Les lymphocytes circulants pourraient représenter un biomarqueur prédictif notamment via la mesure du ratio polynucléaires neutrophiles sur lymphocytes (NLR), ratio simple à réaliser en pratique courante. Un taux de néoantigènes élevé serait également associé à une réponse plus importante ce qui expliquerait les taux de réponses particulièrement élevés des tumeurs avec instabilité micro-satellitaire. Des signatures génomiques pourraient également prédire la sensibilité aux anti-PD1. Par ailleurs, la présence de certaines bactéries de la flore intestinale favoriserait la réponse immunitaire antitumorale même si le mécanisme demeure mal compris. Enfin, des signatures d’expression de cytokines, médiatrices de la réponse immune, pourraient constituer des biomarqueurs pertinents. Plusieurs biomarqueurs de réponse potentiels semblent donc intéressants mais aucun n’est encore prospectivement validé à ce jour.
Published: 2018
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192. The Need for a Consensus Next-generation Sequencing Panel for Mature Lymphoid Malignancies

Author: Gilles Salles, Catherine Thieblemont, Vahid Asnafi, Yannick Le Bris, Elizabeth Macintyre, Audrey Gros, Pierre Sujobert, David Sibon, Sarah Huet, Cedric Pastoret, Jean-Philippe Merlio, Clémentine Sarkozy, Fabrice Jardin, Laurence de Leval, Claude Preudhomme, Frederic Davi, Philippe Gaulard, Mary Callanan, Jonchère, Laurent, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Division de cardiologie [CHU Vaudois] (CHUV), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, CHU Henri Mondor, Université Paris-Est Marne-la-Vallée (UPEM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0303 health sciences, lcsh:RC633-647.5, business.industry, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:Diseases of the blood and blood-forming organs, Computational biology, Hematology, DNA sequencing, 03 medical and health sciences, Text mining, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030220 oncology & carcinogenesis, Perspective, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Medicine, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology
Abstract: International audience; Supplemental Digital Content is available in the text.
Published: 2018
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193. Pan-HDAC Inhibitors May Restore PRDM1 Expression in Follicular Lymphoma

Author: Eric Guiheneuf, Mikael Roussel, Fabienne Desmots-Loyer, Thierry Lamy, Francisco Llamas-Gutierrez, Valérie Camara-Clayette, Vincent Ribrag, Cedric Pastoret, Céline Pangault, Karin Tarte, Thierry Fest, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut Gustave Roussy (IGR), Hématopoïèse normale et pathologique (U1170 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Université Paris-Saclay, Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou, and Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunology, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, hemic and lymphatic diseases, PRDM1, Plasma cell differentiation, Centroblasts, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Tumor microenvironment, business.industry, Germinal center, Cell Biology, Hematology, medicine.disease, BCL6, 3. Good health, Cancer research, business, 030215 immunology
Abstract: Follicular lymphoma (FL) arises from a germinal center (GC) B cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with follicular helper T cells (Tfh). Besides BCL2 translocation hallmark, tumor B cells progressively acquire loss-of-function alterations within chromatin organization factor genes. Notably, frequent inactivating mutations in CREBBP acetyltransferase are found in B-cell lymphoma and drive deep epigenetic and transcriptional profile modifications. Our transcriptional analysis on highly purified cell fractions revealed that, conversely to normal GC B cells (centroblasts and centrocytes), primary FL B cells are unable to upregulate the transcription repressor PRDM1 that is required for plasma cell differentiation and maintenance. This defect happens although FL tumor environment is enriched in the potent inducer of PRDM1, IL-21 that we found highly produced by CD4+ Tfhs. In 20 different FLs perfectly characterized at clinical and genetic level, we analyzed their FL cells obtained after purification from the initial tumor. Globally, we found a significant lack of IL-21-mediated PRDM1 response while our control cell line showed a positive increase of PRDM1 expression. We analyzed some of these primary FL tumor cells by qPCR-ChIP to assess BCL6 protein binding at intron 3 of the PRDM1 gene. We found that the lack of PRDM1 response to IL-21 was associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Our data indicated this was especially the case for FLs with nonfunctional CREBBP. We next explored 6 FLs, cells were treated in vitro with vorinostat, a pan-HDAC inhibitor. We found that for FL B cells carrying CREBBP loss-of-function mutations, vorinostat restored partially their PRDM1 response to IL-21 by lowering BCL6 bound to PRDM1. Finally, we wanted to assess this drug effect in the context of FL patients treated with a pan-HDACi. We found 4 patients involved in a phase I/II clinical at the Gustave Roussy Institute in Villejuif and treated with abexinostat, a new and off-label pan-HDAC inhibitor. All the patients presented a progressive FL disease, were heavily pretreated and their tumor were characterized by genomic DNA sequencing. One patient reached a stable complete remission, the drug was discontinued after 4 years of treatment. Among the three other patients, one had an objective 28-month response to the drug before relapse, one a stable disease for seven months while the last one did not response to the drug. For these 3 patients we've got fine needle tumor biopsy when patients re-progressed. Re-biopsies showed an increased expression of plasma cell-identity genes, mainly PRDM1 and XBP1, which underline the progression of FL B cells in the process of differentiation. Altogether, our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat FL patients. Disclosures Ribrag: BMS: Consultancy, Honoraria, Other: travel; argenX: Research Funding; Servier: Consultancy, Honoraria; epizyme: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Research Funding; Roche: Honoraria, Other: travel; Incyte Corporation: Consultancy; pharmamar: Other: travel; Infinity: Consultancy, Honoraria; MSD: Honoraria.
Published: 2018
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194. Superiority of Allogenic Stem Cell Transplantation after Anti-PD1 Therapy over Anti-PD1 Monotherapy Alone in Relapse/Refractory Hodgkin Lymphoma Real World Evidence from the French Early Access Program

Author: Emmanuelle Nicolas-Virelizier, Remy Dulery, Adrien Chauchet, Roch Houot, Jean Marc Schiano de Collela, Herv Ghesquieres, Guillaume Manson, Anna Schmitt, Alain Delmer, Aspasia Stamatoullas, Jean-Baptiste Mear, Cécile Borel, Charles Herbaux, Georges Garnier, Rene-Olivier Casasnovas, Marie-Pierre Moles, Krimo Bouabdallah, Adrian Tempescul, Pauline Brice, Laurent Dercle, Lysiane Molina, Bénédicte Deau-Fisher, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CRLCC Centre Paoli - Calmettes [Marseille], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Princesse Grace [Monaco], CHU Grenoble, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hopital Saint-Louis [AP-HP] (AP-HP), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Real world evidence, Biochemistry, 3. Good health, Transplantation, 03 medical and health sciences, 030104 developmental biology, Internal medicine, medicine, Refractory Hodgkin Lymphoma, Stem cell, Anti pd1, business, ComputingMilieux_MISCELLANEOUS
Abstract: Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Figure 1). At the time of transplantation, 8 patients were in CR, 5 in partial response (PR) and 4 had progressed of whom 3 received a salvage therapy before alloHSCT. Interestingly, 6 out of 7 patients who were not in CR at the time of transplantation (5 PR and 1 progressive disease) converted into a CR after alloHSCT. At the time of analysis, 14 patients were alive and 13 remained disease-free after a median follow-up of 30.4 months. One-year OS and PFS from alloHSCT were 82% and 76%, respectively. Among responding patients (i.e. in CR or PR) after nivolumab monotherapy, those who underwent subsequent alloHSCT (N=13) had a better outcome than those who were not consolidated with alloHSCT (N=35) (Figure 2). In the transplanted group, none of the patients relapsed whereas in the non-transplanted group 60% of the patients relapsed (p Conclusions: Although patients who achieve a CR upon anti-PD1 therapy may experience prolonged remissions, most R/R HL patients treated with anti-PD1 antibody eventually progress or relapse. Our study demonstrates unprecedented disease-free survival in patients undergoing consolidation with alloHSCT after anti-PD1 therapy. Interestingly, alloHSCT post anti-PD1 can convert incomplete responses into CR in most cases. Despite expected toxicities, alloHSCT after anti-PD1 therapy appears manageable and safe in most patients. Our results suggest that consolidation with alloHSCT may represent a good option in patients treated with anti-PD1, notably in patients who are unable to achieve a CR. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Stamatoullas:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Consultancy. Brice:bristol myers squibb: Consultancy, Honoraria. Houot:bristol myers squibb: Consultancy, Honoraria.
Published: 2018
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195. Reference Values for WBC Differential by Hematoflow Analysis

Author: Cedric Pastoret, Beatrice Ly-Sunnaram, Nicolas Lechevalier, Orianne Wagner-Ballon, Marion Magierowicz, Thierry Fest, Bouchra Badaoui, Francis Lacombe, Mikael Roussel, Nicolas Freynet, CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], CHU Henri Mondor, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Adolescent, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Normal values, Workflow, 03 medical and health sciences, Leukocyte Count, Young Adult, 0302 clinical medicine, Reference Values, Statistics, Humans, education, Child, Mathematics, Aged, education.field_of_study, Flagging, Wbc differential, Infant, General Medicine, Middle Aged, Flow Cytometry, 3. Good health, 030220 oncology & carcinogenesis, Reference values, Child, Preschool, Software, 030215 immunology
Abstract: International audience; Objectives - WBC differentials performed using flow cytometry with monoclonal antibodies have been developed in the last decade and are nowadays integrated into the routine workflow of some laboratories. Definition of reference values for each population is required in order to achieve an automatic validation of the results by laboratory software. Methods - We analyzed 584 samples from three hospitals using the Hematoflow solution to define the reference values. Results - Reference values are presented for five groups according to age (0-5, 6-11, 12-19, 20-69, and >69 years). Conclusions - These normal values will be helpful in the definition of relevant threshold for the automatic validation of samples analyzed by flow cytometry and the flagging of pathologic samples.
Published: 2018
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196. Sensitive tumour detection and classification using plasma cell-free DNA methylomes

Author: Zhen Zhao, Tiantian Li, Anna Goldenberg, Olena Kis, John Douglas Mcpherson, Tiago Medina, Jessica Liu, Mark Mansour, Scott V. Bratman, Signy Chow, Rayjean J. Hung, Neil E. Fleshner, Ayelet Borgida, Philippe L. Bedard, Mark D. Minden, Trevor J. Pugh, Yadon Wang, Anna Spreafico, Gordon Fehringer, Steven Gallinger, Michael H.A. Roehrl, Zhuo Chen, Rajat Singhania, Ankur Chakravarthy, David Roulois, Andrea Arruda, Michael M. Hoffman, Ilias Ettayebi, Geoffrey Liu, Ting Ting Wang, Natasha B. Leighl, Tracy Murphy, Catherine A. O’Brien, Dianne Chadwick, Philip C. Zuzarte, Grainne M. O'Kane, Shu Yi Shen, Daniel D. De Carvalho, Princess Margaret Hospital, University of Toronto, Mount Sinai Hospital [Toronto, Canada] (MSH), Memorial Sloane Kettering Cancer Center [New York], Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Toronto General Hospital Research Institute [Canada] (TGHRI), University of Toronto McLaughlin Centre [MC-2015-02], Canadian Institutes of Health Research [CIHR FDN 148430], Ontario Institute for Cancer Research (OICR), Canada Research Chair [950-231346], Princess Margaret Cancer Foundation, Canadian Cancer Society [CCSRI 701717, CCSRI 704716, CCSRI 703827, CCSRI 020214], Cancer Care Ontario Chair of Population Health, Canadian Institutes of Health Research (CIHR New Investigator Salary award) [201512MSH-360794-228629], province of Ontario, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Multidisciplinary, Somatic cell, Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Plasma cell, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, medicine.anatomical_structure, chemistry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA Mutational Analysis, DNA methylation, medicine, Epigenetics, Liquid biopsy, DNA
Abstract: The use of liquid biopsies for cancer detection and management is rapidly gaining prominence1. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited number of recurrent mutations2–5. By contrast, large-scale epigenetic alterations—which are tissue- and cancer-type specific—are not similarly constrained6 and therefore potentially have greater ability to detect and classify cancers in patients with early-stage disease. Here we develop a sensitive, immunoprecipitation-based protocol to analyse the methylome of small quantities of circulating cell-free DNA, and demonstrate the ability to detect large-scale DNA methylation changes that are enriched for tumour-specific patterns. We also demonstrate robust performance in cancer detection and classification across an extensive collection of plasma samples from several tumour types. This work sets the stage to establish biomarkers for the minimally invasive detection, interception and classification of early-stage cancers based on plasma cell-free DNA methylation patterns. An immunoprecipitation-based protocol is developed to analyse DNA methylation in small quantities of circulating cell-free DNA, and can detect and classify cancers in plasma samples from several tumour types.
Published: 2018
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197. CAR T-cells for T-cell malignancies challenges in distinguishing between therapeutic, normal, and neoplastic T-cells

Author: Carl H. June, Melania Tesio, Marion Alcantara, Roch Houot, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania [Philadelphia], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], University of Pennsylvania, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: 0301 basic medicine, Cancer Research, Lymphoma, B-Cell, CAR T-cells, CAR NK-cells, T-Lymphocytes, medicine.medical_treatment, T cell, [SDV]Life Sciences [q-bio], Antigens, CD19, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunotherapy, Adoptive, Article, CD19, 03 medical and health sciences, 0302 clinical medicine, Antigen, Neoplasms, medicine, Animals, Humans, T-cell malignancies, Receptors, Chimeric Antigen, biology, business.industry, Neoplasms therapy, Hematology, Immunotherapy, medicine.disease, Chimeric antigen receptor, 3. Good health, Lymphoma, T-NHL 39 40, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, T-cell lymphoma, Car t cells, business, T-ALL, human activities
Abstract: International audience; Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrated remarkable efficacy for the treatment of B-cell malignancies. The development of CAR T-cells against T-cell malignancies appears more challenging due to the similarities between the therapeutic, normal and malignant T-cells. The obstacles include CAR T-cell fratricide, T-cell aplasia, and contamination of CAR T-cell products with malignant T-cells. Here, we review these challenges and propose solutions to overcome these limitations.
Published: 2018
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198. An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma

Author: Franck Morschhauser, Hervé Tilly, Cédric Ménard, Bettina Fabiani, Roch Houot, Catherine Thieblemont, Krimo Bouabdallah, Karin Tarte, Gilles Salles, Steven Le Gouill, Guillaume Cartron, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Lymphoma, B-Cell, Maximum Tolerated Dose, Clinical Trials and Observations, Immunology, Follicular lymphoma, Administration, Oral, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Antibodies, Monoclonal, Humanized, Biochemistry, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Agents, Immunological, Refractory, Obinutuzumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lenalidomide, Lymphoma, Follicular, Aged, Aged, 80 and over, business.industry, Cell Biology, Hematology, Middle Aged, medicine.disease, 3. Good health, Lymphoma, chemistry, 030220 oncology & carcinogenesis, Rituximab, Female, Neoplasm Recurrence, Local, business, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: International audience; Obinutuzumab is a type II anti-CD20 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity better than rituximab. Given promising results with lenalidomide and rituximab, this phase 1b study assessed the safety and efficacy of lenalidomide combined with obinutuzumab (GALEN). Patients age ≥18 years with relapsed or refractory (R/R) follicular lymphoma (FL) after rituximab-containing therapy received escalating doses (10 [n = 7], 15 [n = 3], 20 [n = 6], and 25 mg [n = 3]) of daily oral lenalidomide on days 1 to 21 of cycle 1 and on days 2 to 22 of cycles 2 to 6 (28-day cycles). Obinutuzumab 1000 mg IV was administered on days 8, 15, and 22 (cycle 1) and on day 1 (cycles 2-6). Dose was escalated in a 3 + 3 design based on dose-limiting toxicity (DLT) during cycle 1 to establish the maximum tolerated dose (MTD). We observed 164 adverse events (AEs), of which 139 were grade 1/2. The most common AEs were constipation (52.6%), neutropenia (47.4%), and asthenia (36.8%); 64.3% (9 of 14) of the grade 3/4 AEs were neutropenia/neutrophil decrease, but without any febrile neutropenia. Four DLTs occurred in 2 patients, all deemed unrelated to treatment. MTD was not reached. Twelve patients (63.2%) responded: 8 complete, 3 unconfirmed complete, and 1 partial response. Oral lenalidomide plus obinutuzumab is well tolerated and effective in R/R FL. The recommended dose of lenalidomide was established at 20 mg based on the risk of grade 3/4 neutropenia from cycle 2. This trial was registered at www.clinicaltrials.gov as #NCT01582776.
Published: 2018
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199. Lower Body Lift in the Massive Weight Loss Patient A New Classification and Algorithm for Gluteal Augmentation

Author: Benoit Chaput, Nathalie Kerfant, Eric Watier, Benoist Menardais, Isabelle Pluvy, Nicolas Bertheuil, CHU Pontchaillou [Rennes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Lift (data mining), business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030230 surgery, Surgical Flaps, Surgery, 03 medical and health sciences, 0302 clinical medicine, Lower body, medicine.anatomical_structure, Weight loss, 030220 oncology & carcinogenesis, Weight Loss, Buttocks, Humans, Medicine, medicine.symptom, business, Algorithms, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018
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200. Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening

Author: Thomas Daix, Estelle Guerin, Elsa Tavernier, Emmanuelle Mercier, Valérie Gissot, Olivier Hérault, Jean-Paul Mira, Florence Dumas, Nicolas Chapuis, Christophe Guitton, Marie C. Béné, Jean-Pierre Quenot, Cindy Tissier, Julien Guy, Gaël Piton, Anne Roggy, Grégoire Muller, Éric Legac, Nicolas de Prost, Mehdi Khellaf, Orianne Wagner-Ballon, Rémi Coudroy, Elodie Dindinaud, Fabrice Uhel, Mikaël Roussel, Thomas Lafon, Robin Jeannet, Frédéric Vargas, Catherine Fleureau, Mickaël Roux, Kaoutar Allou, Philippe Vignon, Jean Feuillard, Bruno François, Adollës Di Vittorio, Sébastien Lachot, Marie-Thérèse Georget, Joelle Hanna, Cédric Bretonnière, Olivier Zambon, Laurent Nicolet, Noëlle Brule, Camille Debord, Yannick Le Bris, Nelly Robillard, Auguste Dargent, Anne Bretagnol, Armelle Mathonnet, Thierry Boulain, François Barbier, Dalila Benzekri, Isabelle Runge, Toufik Kamel, Jérôme Cecchini, Sabrina Bouyer, René Robert, Alexandre Ouattara, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CIC Tours, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Equipe LIPNESS (LNC - U1231) (LIPNESS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Réanimation Médicale [CHR d'Orléans], Centre Hospitalier Régional d'Orléans (CHR), Hématologie Biologique [CHR d'Orléans], Réanimation Médicale [CHU Henri Mondor - APHP] (DHU A-TVB), Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Septiflux Trial Group : Di Vittorio A, Lachot S, Georget MT, Hanna J, Bretonnière C, Zambon O, Nicolet L, Brule N, Debord C, Le Bris Y, Robillard N, Dargent A, Bretagnol A, Mathonnet A, Boulain T, Barbier F, Benzekri D, Runge I, Kamel T, Cecchini J, Bouyer S, Robert R, Ouattara A., Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Hospitalier Régional d'Orléans (CHRO), CHU Henri Mondor-Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine)-CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Degauque, Nicolas, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and CHU Henri Mondor [Créteil]-Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine)
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Organ Dysfunction Scores, medicine.medical_treatment, Inflammation, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Sepsis, sepsis, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, Prospective Studies, Simplified Acute Physiology Score, Aged, immunosuppression, Clinical Deterioration, Immature Granulocyte, business.industry, Septic shock, flow cytometry, Area under the curve, 030208 emergency & critical care medicine, Immunosuppression, medicine.disease, Survival Analysis, 3. Good health, Systemic inflammatory response syndrome, inflammation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, prognosis, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Background In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. Methods Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. Results Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P =.07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P andlt;.01) and late (P andlt;.01) death. Conclusions Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. Trial Registry ClinicalTrials.gov; No. NCT01995448; URL www.clinicaltrials.gov © 2018 American College of Chest Physicians
Published: 2018
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