A5009250443- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- NF-κB Signaling Pathways
- Monoclonal and Polyclonal Antibodies Research
- Nanoplatforms for cancer theranostics
- Signaling Pathways in Disease
- Estrogen and related hormone effects
- Medical Imaging Techniques and Applications
- Cancer, Lipids, and Metabolism
- Immune Response and Inflammation
- Quinazolinone synthesis and applications
- Pancreatic and Hepatic Oncology Research
- Neuroblastoma Research and Treatments
- Mycobacterium research and diagnosis
- Education, Achievement, and Giftedness
- Protein purification and stability
- Synthesis and Biological Evaluation
- Advanced X-ray and CT Imaging
- Animal Genetics and Reproduction
- interferon and immune responses
- Transgenic Plants and Applications
Inserm
2007-2021
Centre d’Immunologie de Marseille-Luminy
2007-2021
Aix-Marseille Université
2007-2021
Centre National de la Recherche Scientifique
2007-2021
Centre National pour la Recherche Scientifique et Technique (CNRST)
2006-2015
Institut National de Recherche en Santé Publique
2015
Centre de Recherche en Neurobiologie - Neurophysiologie de Marseille
2007
Institut de Neurobiologie de la Méditerranée
2006
University of California, San Diego
1995-1997
Fondation ARC pour la Recherche sur le Cancer
1994
Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. They inhibit synthesis of almost all known cytokines several cell surface molecules required for immune function, but mechanism underlying this activity has been unclear. Here it is shown that glucocorticoids inhibitors nuclear factor kappa B (NF-κB) activation in mice cultured cells. This inhibition mediated by induction IκBα inhibitory protein, which traps activated NF-κB inactive cytoplasmic...
Experimental and clinical evidence suggests that tumor-associated macrophages (TAMs) play important roles in cancer progression. Here, we have characterized the ontogeny function of TAM subsets a mouse model metastatic ovarian is representative for visceral peritoneal metastasis. We show omentum critical premetastatic niche development invasive disease this define unique subset CD163+ Tim4+ resident omental responsible spread cells. Transcriptomic analysis showed were phenotypically distinct...
Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable of contributing to antitumor immunity. Recent studies have revealed an unprecedented heterogeneity among TAMs both human cancer and experimental models. Nevertheless, we still understand little about the contribution different TAM subsets progression. Here, demonstrate that CD163-expressing specifically maintain immune suppression model melanoma is resistant anti-PD-1 checkpoint therapy....
Significance Mechanisms controlling immune reactivity prevent excessive inflammation and autoimmunity, but generally dampen antitumor activity. The tumor necrosis factor alpha-induced protein 3 gene encoding the A20 protein, a key molecule NF-κB activation, has been linked to development of multiple inflammatory pathologies in humans, some which are recapitulated mice with selective deletion myeloid, dendritic, or B cells. Here, mature conventional T cells presented no detectable pathology....
Conventional type 1 dendritic cells (cDC1s) are critical for antitumor immunity. They acquire antigens from dying tumor and cross-present them to CD8+ T cells, promoting the expansion of tumor-specific cytotoxic cells. However, signaling pathways that govern functions cDC1s in immunogenic tumors poorly understood. Using single-cell transcriptomics examine molecular regulating intratumoral cDC1 maturation, we found nuclear factor κB (NF-κB) interferon (IFN) be highly enriched a subset...
Innate immunity is considered to initiate adaptive antitumor responses. We demonstrate that monoclonal CD8 T lymphocytes reactive tumor Ag P1A on P815 mastocytoma cells provide essential "help" NK for rejection of P1A-deficient tumors. RAG-deficient mice have normal but do not reject either tumor. Reconstitution these with P1A-specific conferred resistance both P1A-expressing and -deficient provided they were present at the same site. Elimination Ag-negative variants required activated...
Abstract Poorly functional effector CD8 T cells are generated in some pathological situations, including responses to weakly antigenic tumors. To identify the molecular bases for such defective differentiation, we monitored gene expression naive monoclonal during TCR ligands of different affinity. We further evaluated whether weak Ags may be improved by addition cytokines. Transient was observed a cluster genes response agonist. Strikingly, stabilized low dose IL-2. This IL-2-sustained...
We have produced a soluble form of mouse alpha beta T-cell antigen receptor (TCR) by shuffling its variable (V) and constant (C) domains to the C region an immunoglobulin kappa light chain. These chimeric molecules composed V chains were efficiently secreted (up 1 micrograms/ml) transfected myeloma cells as noncovalent heterodimers about 95-kDa molecular mass. In absence direct binding measurement, we refined epitopic analysis kappa-V dimers shown that they react with anti-clonotypic...
In adoptive therapy, CD8 T cells expressing active STAT5 (STAT5CA) transcription factors were found to be superior unmanipulated counterparts in long-term persistence, capacity infiltrate autochthonous mouse melanomas, thrive their microenvironment, and induce regression. However, the molecular mechanisms sustaining these properties undefined. this study, we report that STAT5CA induced sustained expression of genes controlling tissue homing, cytolytic granule composition, type 1 cytotoxic...
Abstract The fate of the T cell receptor (TcR)/CD3 complex was examined on a cytotoxic lymphocyte (CTL) clone (KB5.C20) activated either via binding an anti‐TcR monoclonal antibody (mAb) or by Ca 2+ ionophore and phorbol 12‐myristate 13‐acetate (PMA). After mAb, electron microscopy revealed internalization through coated vesicles followed slow degradation as shown use radiolabeled mAb. influence activation TcR/CD3 analyzed. alone had no effect internalization, whereas PMA induced accelerated...
Immunotherapy based on adoptive transfer of tumor antigen-specific CD8(+) T cell (TC) is generally limited by poor in vivo expansion and infiltration. In this study, we report that activated STAT5 transcription factors (STAT5CA) confer high efficiency effector cells (eTC) for host colonization after transfer. Engineered expression STAT5CA antigen-experienced TCs with replicative potential was also sufficient to convert them into long-lived antigen-responsive eTCs. transplanted mastocytoma-...
Migration of dendritic cells (DC) from the tumor environment to T cell cortex in tumor-draining lymph nodes (TDLN) is essential for priming naïve lymphocytes (TL) antigen (Ag). We used a mouse model induced melanoma which similar oncogenic events generate two phenotypically distinct melanomas study influence tumor-associated inflammation on secondary lymphoid organ (SLO) organization. One promotes inflammatory cytokines, leading mobilization immature myeloid (iMC) and SLO; other does not....
Abstract To examine the bases for CD8 T cell functional heterogeneity, we analyzed responses to partial vs full agonist Ag. An extended period of interaction with APCs was required set threshold division in response as compared Acquisition cytolytic function restricted divided population. In contrast, commitment produce IFN-γ and express some activation markers appeared lower independent division. Indeed, characterized a population stimulated that committed IFN-γ, but failed divide or...
We investigated the requirements of positive and negative selection in thymus for CD8 interaction selecting cell type. Thymic epithelial cells are known to mediate selection, whereas thymocytes fail do so. The reason this failure could be either low amount MHC class I molecules on or lack other properties required selection. To address question a CD2.Kb transgenic mouse was prepared which expression Kb gene is under control CD2 promoter. In these mice exhibited very high levels Kb. were...
Although much has been learned about CD8 structure-function properties, it so far not tested whether the nature of TCR is sufficient to transfer property dependence versus non-dependence CD8+ cytotoxic T lymphocytes (CTL) and their precursors differentiating in cell receptor (TCR)-transgenic (Tg) mice. In present study, we compared characteristics on for stimulation CTL antigen-specific cytolysis by cells from two TCR-Tg mice expressing respectively a “CD8-dependent” “CD8-independent” clone,...
Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8+ T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development autochthonous melanomas in TiRP mice that develop tumors expressing known antigen as well red fluorescent protein (RFP) reporter knock gene. The latter permits non-invasive monitoring growth biofluorescence. One developing melanoma was deficient cell surface MHC-I, but MHC-I could...
Abstract As shown previously, a given cytotoxic T lymphocyte (CTL) clone (KB5.C20) could be induced to express the Fas ligand (FasL) by either cell receptor (TCR) engagement or phorbol 12‐myristate 13‐acetate (PMA)/ionomycin stimulation. In contrast, another CTL (BM3.3) has now been found exert Fas‐based cytotoxicity only after TCR engagement, but not PMA/ionomycin This suggested existence of PMA‐insensitive, antigeninduced pathway leading FasL expression. The inability PMA promote in BM3.3...
Exposure to microbe-associated molecular patterns (MAMPs) causes dendritic cells (DCs) undergo a remarkable activation process characterized by changes in key biochemical mechanisms. These enhance antigen processing and presentation, as well strengthen DC capacity stimulate naïve T cell proliferation. Here, we show that response the MAMPS lipopolysaccharide polyriboinosinic:polyribocytidylic acid (Poly I:C), RNA polymerase III (Pol lII)-dependent transcription consequently tRNA gene...
Abstract Tolerant T cells are characterized by their partial or full resistance to activation antigen. We investigated whether tolerant were still receptive further tolerogenic signals. expressing a transgenic cell receptor (TCR) specific for the major histocompatibility complex (MHC) class I molecule K b deleted in mice carrying but not mutant ‐molecule bm1 [TCR (H‐2 × k ) mice]. These vivo could be activated vitro This reactivity was abolished after encountered ‐positive that had been...