A5046055450- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- FOXO transcription factor regulation
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Diabetes and associated disorders
- IL-33, ST2, and ILC Pathways
- Immunodeficiency and Autoimmune Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Peptidase Inhibition and Analysis
- Inflammasome and immune disorders
- PARP inhibition in cancer therapy
- Chemokine receptors and signaling
- Cancer-related molecular mechanisms research
Centre de Recherche en Cancérologie de Toulouse
2018-2024
Inserm
2012-2024
Université Toulouse III - Paul Sabatier
2009-2024
Centre National de la Recherche Scientifique
2012-2024
Centre National pour la Recherche Scientifique et Technique (CNRST)
2024
Centre de Physiopathologie de Toulouse-Purpan
2009-2016
Université de Toulouse
2012-2016
Institut universitaire du cancer de Toulouse Oncopole
2016
Hôpital Purpan
2009
CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by and its role in immune surveillance remain unresolved. Using T cell-specific deletion agonist antibodies, we found that modulates tumor infiltration of CD8+-exhausted (Tex) cells expressing PD1, Lag-3, Tim-3 inhibitory receptors. cell-intrinsic, TCR-independent signaling stimulated proliferation terminal differentiation Tex precursor through mechanism involving RelA...
T cells differentiate into functionally distinct effector subsets in response to pathogen encounter. Cells of the innate immune system direct this process; CD1d-restricted invariant natural killer (iNKT) cells, for example, can either promote or inhibit Th(1) and Th(2) responses. Recently, a new subset CD4(+) helper called Th(17), was identified that is implicated mucosal immunity autoimmune disorders. To investigate influence iNKT on differentiation naïve we used an adoptive transfer model...
Abstract An increase in IL-17–producing CD8+ T (Tc17) cells has been reported the peripheral blood of children with recent onset type 1 diabetes (T1D), but their contribution to disease pathogenesis is still unknown. To directly study pathogenic potential β cell-specific Tc17 cells, we used an experimental model T1D based on expression neo-self Ag hemagglutinin (HA) pancreas. When transferred alone, HA-specific homed pancreatic lymph nodes without causing any infiltration or tissue...
Abstract Anti-CD38 monoclonal antibodies (mAbs) represent a breakthrough in the treatment of multiple myeloma (MM), yet some patients fail to respond or progress quickly with this therapy, highlighting need for novel approaches. In study we compared preclinical efficacy SAR442085, next-generation anti-CD38 mAb enhanced affinity activating Fcγ receptors (FcγR), first-generation daratumumab and isatuximab. surface plasmon resonance cellular binding assays, found that SAR442085 had higher than...
The promising results obtained with immunotherapeutic approaches for multiple myeloma (MM) call a better stratification of patients based on immune components. most pressing being cytotoxic lymphocytes such as natural killer (NK) cells that are mandatory MM surveillance and therapy. Here, we performed single-cell RNA sequencing analysis NK from 10 age/sex-matched healthy donors revealed important transcriptomic changes in the cell landscape affecting both bone marrow (BM) peripheral blood...
Polyspecific T cells recognizing multiple distinct self-antigens have been identified in sclerosis and other organ-specific autoimmune diseases, but their pathophysiological relevance remains undetermined. Using a mouse model of sclerosis, we show that encephalomyelitis induction is strictly dependent on reactivation pathogenic by peptide (35-55) derived from myelin oligodendrocyte glycoprotein (MOG). This disease-inducing response wanes after onset. Strikingly, the progression disease...
The recognition of multiple ligands by a single TCR is an intrinsic feature T cell biology, with important consequences for physiological and pathological processes. Polyspecific cells targeting distinct self-antigens have been identified in healthy individuals as well the context autoimmunity. We previously shown that 2D2 recognizes myelin oligodendrocyte glycoprotein epitope (MOG)35-55 within axonal protein neurofilament medium (NF-M15-35) H-2(b) mice. In this study, we assess whether...
The pathogenesis of multiple sclerosis requires the participation effector neuroantigen-specific T cells. Thus, cell targeting has been proposed as a promising therapeutic strategy. However, mechanism underlying effective disease prevention following remains incompletely known. We found, using several TCR-transgenic strains, that CD4 blockade is in preventing experimental autoimmune encephalopathy and treating mice after onset. does not rely on direct depletion, but anti-CD4 mAb prevents...
Abstract CD4 T cell differentiation is a process finely controlled by specific transcriptional programs leading to the acquisition of helper effector functions. Up now, functions Foxo3 in cells have not been investigate. Here, we described for first time critical role transcription factors Eomes expression and their involvement pathogenic Helper 1 differentiation. First, showed that TCR triggering resulted dose-dependent upregulation with an increased over time. We next addressed observed...
ABSTRACT The promising results obtained with immunotherapeutic approaches for multiple myeloma (MM) call a better stratification of patients based on immune components. most pressing being cytotoxic lymphocytes such as Natural Killer (NK) cells that are mandatory MM surveillance and therapy. In this study, we performed single cell RNA sequencing analysis NK from 10 age/sex matched healthy donors (HD) revealed important transcriptomic changes in landscape affecting both the bone marrow...
Abstract Despite recent breakthrough in the treatment of multiple myeloma (MM) relapses are frequent, highlighting need for novel approaches. Here we describe a anti-CD38/CD28xCD3 trispecific T cell engager (TCE) that targets CD38 expressed by malignant plasma cells and activates engaging CD3 CD28 (1). Using bone marrow (BM) aspirates from MM patients, confirmed binding to plasmocytes is primarily driven expression showed ex vivo CD38/CD28xCD3 TCE induces dose-dependent proliferation CD4+...
Abstract The Foxo3 transcription factor regulates cell cycle progression, survival and DNA repair pathways. In addition to its role as a tumor suppressor gene, studies have established the crucial of in immune cells, notably dendritic cells CD8 T context viral infection. However, CD4 function is still unknown. Here, we show that expression levels are increased after TCR engagement. We also deficiency leads decreased secretion IFN-γ GM-CSF but not IL-17. By dissecting underlying molecular...
Abstract Foxo proteins control gene expression during many cellular processes including cell cycle progression, reactive oxygen species detoxification, survival and death. During viral infection, we demonstrated that Foxo3 critically down-regulates the magnitude of anti-viral T response by constraining production key inflammatory cytokines dendritic cells (DCs). This impact on innate immune suggests is likely to intensity adaptive irrespective its nature. We therefore analyze implication in...
Although anti-PD-1 and anti-CTLA-4 based immune checkpoint blockade (ICB) has represented a turning point in cancer care, clinical responses are observed only fraction of patients. Most research focuses on the identification additional inhibitory receptors restraining anti-tumor functions CD8+ T cells. By contrast, herein, we found that loss activating receptor CD226 (DNAM-1) was critical mechanism affecting cell responsiveness to TCR stimulation. Using patients’ samples preclinical mouse...
CD137 (4-1BB) activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by and its role in immunosurveillance remain to be addressed. Here, we found that agonists rapidly induced CD8+ T cell chromatin remodeling expression of exhausted (Tex) specific genes. cell-intrinsic, TCR independent, signaling involving RelA cRel NF-kB subunits stimulated expansion Tex cells characterized multiple immune checkpoints (PD1, Tim3, Tigit) reduced effector...