8 results on '"Grazia, Locafaro"'
Search Results
2. Monitoring T-Cell Responses in Translational Studies: Optimization of Dye-Based Proliferation Assay for Evaluation of Antigen-Specific Responses
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Anja Ten Brinke, Natalia Marek-Trzonkowska, Maria J. Mansilla, Annelies W. Turksma, Karolina Piekarska, Dorota Iwaszkiewicz-Grześ, Laura Passerini, Grazia Locafaro, Joan Puñet-Ortiz, S. Marieke van Ham, Maria P. Hernandez-Fuentes, Eva M. Martínez-Cáceres, and Silvia Gregori
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tolerance ,monitoring ,proliferation ,antigen-specific ,T cells ,transplantation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Adoptive therapy with regulatory T cells or tolerance-inducing antigen (Ag)-presenting cells is innovative and promising therapeutic approach to control undesired and harmful activation of the immune system, as observed in autoimmune diseases, solid organ and bone marrow transplantation. One of the critical issues to elucidate the mechanisms responsible for success or failure of these therapies and define the specificity of the therapy is the evaluation of the Ag-specific T-cell responses. Several efforts have been made to develop suitable and reproducible assays. Here, we focus on dye-based proliferation assays. We highlight with practical examples the fundamental issues to take into consideration for implementation of an effective and sensitive dye-based proliferation assay to monitor Ag-specific responses in patients. The most critical points were used to design a road map to set up and analyze the optimal assay to assess Ag-specific T-cell responses in patients undergoing different treatments. This is the first step to optimize monitoring of tolerance induction, allowing comparison of outcomes of different clinical studies. The road map can also be applied to other therapeutic interventions, not limited to tolerance induction therapies, in which Ag-specific T-cell responses are relevant such as vaccination approaches and cancer immunotherapy.
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- 2017
- Full Text
- View/download PDF
3. HLA-G Expression on Blasts and Tolerogenic Cells in Patients Affected by Acute Myeloid Leukemia
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Grazia Locafaro, Giada Amodio, Daniela Tomasoni, Cristina Tresoldi, Fabio Ciceri, and Silvia Gregori
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Human Leukocyte Antigen-G (HLA-G) contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role of HLA-G expression and functions in Acute Myeloid Leukemia (AML) is still controversial. Our group identified a subset of tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10 are present in the peripheral blood and are essential in promoting and maintaining tolerance via the induction of adaptive T regulatory (Treg) cells. We investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC-10 and CD4+ T cells in the peripheral blood of AML patients at diagnosis. Moreover, we explored the possible influence of the 3′ untranslated region (3′UTR) of HLA-G, which has been associated with HLA-G expression, on AML susceptibility. Results showed that HLA-G-expressing DC-10 and CD4+ T cells are highly represented in AML patients with HLA-G positive blasts. None of the HLA-G variation sites evaluated was associated with AML susceptibility. This is the first report describing HLA-G-expressing DC-10 and CD4+ T cells in AML patients, suggesting that they may represent a strategy by which leukemic cells escape the host’s immune system. Further studies on larger populations are required to verify our findings.
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- 2014
- Full Text
- View/download PDF
4. Emotional outcomes in clinically isolated syndrome and early phase multiple sclerosis: a systematic review and meta-analysis
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Inez Myin-Germeys, J. Devonshire, Faith Matcham, Marta Radaelli, Sara Simblett, Giancarlo Comi, J. Weyer, Grazia Locafaro, Matthew Hotopf, Aki Rintala, C Barattieri di San Pietro, Til Wykes, Viola Bulgari, P. Burke, Rintala, A, Matcham, F, Radaelli, M, Locafaro, G, Simblett, S, Barattieri di San Pietro, C, Bulgari, V, Burke, P, Devonshire, J, Weyer, J, Wykes, T, Comi, G, Hotopf, M, and Myin-Germeys, I
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Multiple Sclerosis ,IMPACT ,DISORDERS ,DIAGNOSTIC-CRITERIA ,Emotions ,Hospital Anxiety and Depression Scale ,M-PSI/02 - PSICOBIOLOGIA E PSICOLOGIA FISIOLOGICA ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,QUALITY-OF-LIFE ,Depressive syntoms, Anxiety symptoms, Multiple sclerosis, Quality of life ,medicine ,ANXIETY ,Humans ,030212 general & internal medicine ,Depression (differential diagnoses) ,Psychiatry ,Clinically isolated syndrome ,Science & Technology ,business.industry ,DISABILITY ,MS ,medicine.disease ,COGNITIVE IMPAIRMENT ,Quality of Life ,Suicide ,3. Good health ,Psychiatry and Mental health ,Clinical Psychology ,Systematic review ,Meta-analysis ,DEPRESSIVE SYMPTOMS ,Anxiety ,MED/25 - PSICHIATRIA ,medicine.symptom ,business ,FOLLOW-UP ,Life Sciences & Biomedicine ,030217 neurology & neurosurgery ,Anxiety disorder ,Clinical psychology - Abstract
OBJECTIVE: To study depression, anxiety, suicide risk, and emotional health-related quality of life (HRQoL) in people with clinically isolated syndrome (CIS) and in early phase multiple sclerosis (MS). METHODS: A systematic literature review was conducted with inclusion criteria of observational studies on outcomes of depression, anxiety, suicide risk, and emotional HRQoL in CIS and within five years since diagnosis of MS. Studies were screened using the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, and study quality was determined for included studies. Meta-analysis and meta-regression were performed if applicable. RESULTS: Fifty-one studies were included in the systematic review. In early phase MS, meta-analyses of the Hospital Anxiety Depression Scale (HADS) indicated prevalence levels of 17% (95% confidence interval (CI): 9 to 25%; p
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- 2019
5. IL-10-Engineered Human CD4
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Grazia, Locafaro, Grazia, Andolfi, Fabio, Russo, Luca, Cesana, Antonello, Spinelli, Barbara, Camisa, Fabio, Ciceri, Angelo, Lombardo, Attilio, Bondanza, Maria Grazia, Roncarolo, and Silvia, Gregori
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CD4-Positive T-Lymphocytes ,surgical procedures, operative ,tolerance ,immune system diseases ,Leukemia, Myeloid ,Leukocytes, Mononuclear ,Humans ,Original Article ,immunotherapy ,gene transfer ,Models, Biological ,T-Lymphocytes, Regulatory ,Interleukin-10 - Abstract
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4+ T cells into T regulatory type 1 (Tr1)-like (CD4IL-10) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models. In the present study, we show that CD4IL-10 cells mediate anti-leukemic effects in vitro and in vivo in a human leukocyte antigen (HLA) class I-dependent but antigen-independent manner. The cytotoxicity mediated by CD4IL-10 cells is granzyme B (GzB) dependent, is specific for CD13+ target cells, and requires CD54 and CD112 expression on primary leukemic target blasts. CD4IL-10 cells adoptively transferred in humanized mouse models directly mediate anti-tumor and anti-leukemic effects. In addition, when co-transferred with peripheral blood mononuclear cells (PBMCs), CD4IL-10 cells contribute to the GvL activity but suppress xenoGvHD mediated by the PBMCs. These findings provide for the first time a strong rationale for CD4IL-10 cell immunotherapy to prevent GvHD and promote GvL in allo-HSCT for myeloid malignancies., Graphical Abstract, Tr1 cells are generated by overexpressing IL-10 in CD4+ T cells (CD4IL-10). In this issue of Molecular Therapy, Locafaro et al. (2017) show that CD4IL-10 cells kill myeloid leukemia in an HLA class I-dependent mechanism, mediate anti-tumor and anti-leukemic effects, and contribute to GvL while preventing GvHD in humanized mice.
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- 2017
6. IL-10-Engineered Human CD4+ Tr1 Cells Eliminate Myeloid Leukemia in an HLA Class I-Dependent Mechanism
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Fabio Ciceri, Antonello E. Spinelli, Fabio Russo, Barbara Camisa, Angelo Lombardo, Grazia Andolfi, Maria Grazia Roncarolo, Luca Cesana, Silvia Gregori, Attilio Bondanza, Grazia Locafaro, Locafaro, Grazia, Andolfi, Grazia, Russo, Fabio, Cesana, Luca, Spinelli, Antonello, Camisa, Barbara, Ciceri, Fabio, Lombardo, ANGELO LEONE, Bondanza, Attilio, Roncarolo, MARIA GRAZIA, and Gregori, Silvia
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0301 basic medicine ,Myeloid ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,Biology ,03 medical and health sciences ,Genetic ,immune system diseases ,Drug Discovery ,Genetics ,medicine ,Gene transfer ,Molecular Biology ,Pharmacology ,Drug Discovery3003 Pharmaceutical Science ,Myeloid leukemia ,Immunotherapy ,Granzyme B ,Interleukin 10 ,surgical procedures, operative ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Humanized mouse ,Molecular Medicine ,Tolerance - Abstract
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4+ T cells into T regulatory type 1 (Tr1)-like (CD4IL-10) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models. In the present study, we show that CD4IL-10 cells mediate anti-leukemic effects in vitro and in vivo in a human leukocyte antigen (HLA) class I-dependent but antigen-independent manner. The cytotoxicity mediated by CD4IL-10 cells is granzyme B (GzB) dependent, is specific for CD13+ target cells, and requires CD54 and CD112 expression on primary leukemic target blasts. CD4IL-10 cells adoptively transferred in humanized mouse models directly mediate anti-tumor and anti-leukemic effects. In addition, when co-transferred with peripheral blood mononuclear cells (PBMCs), CD4IL-10 cells contribute to the GvL activity but suppress xenoGvHD mediated by the PBMCs. These findings provide for the first time a strong rationale for CD4IL-10 cell immunotherapy to prevent GvHD and promote GvL in allo-HSCT for myeloid malignancies. Tr1 cells are generated by overexpressing IL-10 in CD4+ T cells (CD4IL-10). In this issue of Molecular Therapy, Locafaro et al. (2017) show that CD4IL-10 cells kill myeloid leukemia in an HLA class I-dependent mechanism, mediate anti-tumor and anti-leukemic effects, and contribute to GvL while preventing GvHD in humanized mice.
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- 2017
7. HLA-G Expression on Blasts and Tolerogenic Cells in Patients Affected by Acute Myeloid Leukemia
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Silvia Gregori, Daniela Tomasoni, Giada Amodio, Grazia Locafaro, Fabio Ciceri, Cristina Tresoldi, Locafaro, G, Amodio, G, Tomasoni, D, Tresoldi, C, Ciceri, Fabio, and Gregori, S.
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lcsh:Immunologic diseases. Allergy ,Adult ,Male ,Article Subject ,Immunology ,Gene Expression ,Human leukocyte antigen ,Biology ,T-Lymphocytes, Regulatory ,Immune tolerance ,Immune system ,HLA-G ,hemic and lymphatic diseases ,Immune Tolerance ,Immunology and Allergy ,Humans ,3' Untranslated Regions ,Aged ,Immune Evasion ,Aged, 80 and over ,HLA-G Antigens ,Three prime untranslated region ,Myeloid leukemia ,General Medicine ,Dendritic Cells ,Middle Aged ,Interleukin-10 ,Interleukin 10 ,Leukemia, Myeloid, Acute ,Cancer cell ,Female ,Disease Susceptibility ,lcsh:RC581-607 ,Research Article - Abstract
Human Leukocyte Antigen-G (HLA-G) contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role of HLA-G expression and functions in Acute Myeloid Leukemia (AML) is still controversial. Our group identified a subset of tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10 are present in the peripheral blood and are essential in promoting and maintaining tolerance via the induction of adaptive T regulatory (Treg) cells. We investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC-10 and CD4+T cells in the peripheral blood of AML patients at diagnosis. Moreover, we explored the possible influence of the 3′ untranslated region (3′UTR) ofHLA-G, which has been associated with HLA-G expression, on AML susceptibility. Results showed that HLA-G-expressing DC-10 and CD4+T cells are highly represented in AML patients with HLA-G positive blasts. None of the HLA-G variation sites evaluated was associated with AML susceptibility. This is the first report describing HLA-G-expressing DC-10 and CD4+T cells in AML patients, suggesting that they may represent a strategy by which leukemic cells escape the host’s immune system. Further studies on larger populations are required to verify our findings.
- Published
- 2014
8. 637. Targeting of Myeloid Leukemia by IL-10-Engineered Human CD4+ Tr1 Cells
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Fabio Russo, Silvia Gregori, Maria Grazia Roncarolo, Grazia Locafaro, Barbara Camisa, Angelo Lombardo, Fabio Ciceri, Attilio Bondanza, and Grazia Andolfi
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Pharmacology ,CD40 ,CD1 ,Biology ,Natural killer T cell ,Interleukin 21 ,NK-92 ,Drug Discovery ,Immunology ,Genetics ,Cancer research ,biology.protein ,Molecular Medicine ,Cytotoxic T cell ,Antigen-presenting cell ,Molecular Biology ,Interleukin 3 - Abstract
T regulatory type 1 (Tr1) cells, characterized by the co-expression of CD49b and LAG-3 and the ability to secrete high amounts of IL-10, control immune responses by IL-10 and TGF-beta production and by killing of myeloid cells via a Granzyme B-dependent mechanism. Tr1 cells are induced in vitro in the presence of recombinant human IL-10 or tolerogenic dendritic cells secreting high amounts of IL-10 (DC-10). Proof-of-principle clinical trials suggest that Tr1 cells can modulate Graft-versus Host Disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity or their effects of Graft versus Leukemia is largely unknown. We previously showed that enforced IL-10 expression converts human CD4+ T cells into Tr1-like (CD4IL-10) cells that suppress effector T cells in vitro and prevent xenogeneic-GvHD in humanized models. We now demonstrate that these CD4IL-10 cells selectively kill myeloid cell lines and myeloid blasts in vitro in HLA-class I-dependent but antigen-independent manner. Moreover, cytotoxic activity of CD4IL-10 cells is Granzyme B-dependent, is specific for CD13+ cells, and requires CD54 and CD112 expression on target cell lines or primary leukemic blast. Adoptive transfer of CD4IL-10 cells in humanized models mediates direct anti-leukemic activity, and does not compromise the anti-leukemic effect of allogeneic T cells while inhibits xeno-GvHD. These findings provide a strong rationale for designing personalized immunotherapy approaches using CD4IL-10 cells after allo-HSCT to cure myeloid malignancies.
- Published
- 2016
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