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2 results on '"Florent Creusat"'

1. Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities

Author

Baptiste Brauge, Elise Dessauge, Florent Creusat, and Karin Tarte

Subjects
tumor microenvironment, follicular lymphoma, diffuse large B-cell lymphoma, germinal center, stromal cells, 3D models, Immunologic diseases. Allergy, RC581-607
Abstract

B-cell lymphomas are a group of heterogeneous neoplasms resulting from the clonal expansion of mature B cells arrested at various stages of differentiation. Specifically, two lymphoma subtypes arise from germinal centers (GCs), namely follicular lymphoma (FL) and GC B-cell diffuse large B-cell lymphoma (GCB-DLBCL). In addition to recent advances in describing the genetic landscape of FL and GCB-DLBCL, tumor microenvironment (TME) has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, and late progression/transformation. The lymphoma-supportive niche integrates a dynamic and coordinated network of immune and stromal cells defining microarchitecture and mechanical constraints and regulating tumor cell migration, survival, proliferation, and immune escape. Several questions are still unsolved regarding the interplay between lymphoma B cells and their TME, including the mechanisms supporting these bidirectional interactions, the impact of the kinetic and spatial heterogeneity of the tumor niche on B-cell heterogeneity, and how individual genetic alterations can trigger both B-cell intrinsic and B-cell extrinsic signals driving the reprogramming of non-malignant cells. Finally, it is not clear whether these interactions might promote resistance to treatment or, conversely, offer valuable therapeutic opportunities. A major challenge in addressing these questions is the lack of relevant models integrating tumor cells with specific genetic hits, non-malignant cells with adequate functional properties and organization, extracellular matrix, and biomechanical forces. We propose here an overview of the 3D in vitro models, xenograft approaches, and genetically-engineered mouse models recently developed to study GC B-cell lymphomas with a specific focus on the pros and cons of each strategy in understanding B-cell lymphomagenesis and evaluating new therapeutic strategies.

Published
2023
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2. Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction

Author

Florian Reizine, Murielle Grégoire, Mathieu Lesouhaitier, Valentin Coirier, Juliette Gauthier, Céline Delaloy, Elise Dessauge, Florent Creusat, Fabrice Uhel, Arnaud Gacouin, Frédéric Dessauge, Cécile Le Naoures, Caroline Moreau, Claude Bendavid, Yoann Daniel, Kilian Petitjean, Valérie Bordeau, Claire Lamaison, Caroline Piau, Vincent Cattoir, Mikael Roussel, Bernard Fromenty, Christian Michelet, Yves Le Tulzo, Jaroslaw Zmijewski, Ronan Thibault, Michel Cogné, Karin Tarte, Jean-Marc Tadié, 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], Etablissement Français du Sang Bretagne, EFS, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ARN régulateurs bactériens et médecine (BRM), Centre National de Référence de la Résistance aux Antibiotiques [CHU Rennes] (CNR), University of Alabama at Birmingham [ Birmingham] (UAB), This work was supported by funding from the Société de Réanimation de Langue Française (SRLF, Bourses Master 2 SRLF). We also thank the animal house Animalerie Rennaise Centre d’Hébergement et d’Expérimentation (ARCHE) platform and H2P2 platform (Structure Fédérative de Recherche [SFR] Biosit), and Aude Bodin for her help with mitochondrial functions analysis., Jonchère, Laurent, and Center of Experimental and Molecular Medicine

Subjects
Immunosuppression Therapy, Multidisciplinary, Myeloid-Derived Suppressor Cells, T-Lymphocytes, [SDV]Life Sciences [q-bio], Biological Availability, T cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Arginine, Lymphocyte Activation, T-Lymphocytes, Regulatory, Mitochondria, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Disease Models, Animal, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Sepsis, Immune Tolerance, Animals, Cytokines, Citrulline, Female
Abstract

International audience; Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.

Published
2022

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