A5023263627- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Cancer Cells and Metastasis
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Colorectal Cancer Treatments and Studies
- Immune Response and Inflammation
- Colorectal Cancer Surgical Treatments
- Immune cells in cancer
- Gastrointestinal Tumor Research and Treatment
- Chemokine receptors and signaling
- Lymphoma Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Chronic Myeloid Leukemia Treatments
- Extracellular vesicles in disease
- Polyomavirus and related diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Ovarian cancer diagnosis and treatment
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- interferon and immune responses
- NF-κB Signaling Pathways
Inserm
2014-2024
Université Paris Cité
2013-2024
Paris Cardiovascular Research Center
2015-2024
Sorbonne Paris Cité
2012-2024
La Ligue Contre le Cancer
2017-2021
Hôpital Européen Georges-Pompidou
2012-2021
Assistance Publique – Hôpitaux de Paris
2021
Délégation Paris 5
2011-2019
Centre National de la Recherche Scientifique
2011-2016
Nantes Université
2016
Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which characterized by expression of inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and progressive loss function. The recent development therapies targeting PD-1 CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, regulation expression, thereby...
Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and reg in tumor-bearing patients, shown here, prompted us to address role controlling innate antitumor immunity. Our experiments indicate human expressed membrane-bound transforming factor (TGF)–β, which directly inhibited NK effector functions down-regulated NKG2D receptors on surface. Adoptive...
Multitarget antiangiogenic tyrosine kinase inhibitors (TKI) have been shown to reduce regulatory T cells (Treg) in tumor-bearing animals and patients with metastatic renal carcinomas. However, a direct role of the VEGF-A/VEGFR pathway inhibition this phenomenon is matter debate molecular mechanisms leading Treg modulation setting not explored date. proportion, number, proliferation were analyzed by flow cytometry peripheral blood colorectal cancer (mCRC) treated bevacizumab, monoclonal...
Dendritic cell (DC) derived-exosomes (Dex) are nanomeric vesicles harboring functional MHC/peptide complexes promoting T cell-dependent tumor rejection. In the first Phase I trial using peptide-pulsed Dex, observation of clinical regressions in absence responses prompted search for alternate effector mechanisms. Mouse studies unraveled bioactivity Dex on NK cells. Indeed, promoted an IL-15Ralpha- and NKG2D-dependent proliferation activation respectively, resulting anti-metastatic effects...
Abstract Immunosuppressive cytokines subvert innate and adaptive immune responses during cancer progression. The inflammatory cytokine interleukin-18 (IL-18) is known to accumulate in patients, but its pathophysiological role remains unclear. In this study, we show that low levels of circulating IL-18, either exogenous or tumor derived, act suppress the NK cell arm immunosurveillance. IL-18 produced by cells promotes development NK-controlled metastases a PD-1–dependent manner. Accordingly,...
Abstract Tissue-resident memory T cells (Trm) represent a new subset of long-lived that remain in tissue and do not recirculate. Although they are considered as early immune effectors infectious diseases, their role cancer immunosurveillance remains unknown. In preclinical model head neck cancer, we show intranasal vaccination with mucosal vector, the B subunit Shiga toxin, induces local Trm inhibits tumour growth. As recirculate, demonstrate crucial efficacy vaccine parabiosis experiments....
Mucosal vaccination induces targeted CD8 + T cell homing to inhibit mucosal tumors.
Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor these tyrosine kinase receptors. Case reports clinical efficacy Gleevec in GISTs lacking typical receptor mutations prompted search an alternate mode action. Here we show that can act on host DCs to promote NK cell activation. DC-mediated activation was triggered vitro and vivo treatment with as well...
Abstract Dendritic cell-derived exosomes (DEX) are nanomeric vesicles harboring MHC/peptide complexes capable of promoting primary T cell responses and tumor rejection in the presence adjuvants. In this study, we show that, absence adjuvants, DEX mediate potent Ag-dependent antitumor effects against preestablished tumors mice pretreated with immunopotentiating dosing cyclophosphamide. Cyclophosphamide could 1) abolish suppressive function CD4+CD25+Foxp3+ regulatory cells, 2) markedly enhance...
During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression NK cell-controlled cancers, mechanistic cues underlying this immunosuppression remain unknown. Here, we show IL-18 converts subset Kit(-) (CD11b(-)) into Kit(+) natural killer (NK) cells, which accumulate all lymphoid organs bearers mediate...
Many cancer cells express Toll-like receptors (TLR) that offer possible therapeutic targets. Polyadenylic-polyuridylic acid [poly(A:U)] is an agonist of the receptor TLR3 displays anticancer properties. In this study, we illustrate how immunostimulatory and immunosuppressive effects agent can be uncoupled to advantage. We took advantage two TLR3-expressing tumor models produced large amounts CCL5 (a CCR5 ligand) CXCL10 CXCR3 in response type I IFN poly(A:U), both vitro vivo. Conventional...
CD4+CD25+Foxp3+ regulatory T cells (Treg) have emerged as a dominant cell population inhibiting anti-tumor effector cells. Initial strategies used for Treg-depletion (cyclophosphamide, anti-CD25 mAb…) also targeted activated cells, they share many phenotypic markers. Current, ameliorated approaches to inhibit Treg aim either block their function or migration lymph nodes and the tumor microenvironment. Various drugs originally developed other therapeutic indications (anti-angiogenic...
Abstract The CD4+CD25+Foxp3+ regulatory T cells (Treg) play an important role in the control of peripheral tolerance by directly inhibiting conventional cell proliferative and effector functions. However, mechanisms which Treg regulate homeostasis lymph nodes remain unclear. In this study, we show a mouse model that two major checkpoints dictated interaction between self-reactive CD4+ resident dendritic (DC) secondary lymphoid organs. First, inhibit production CCR5 ligands, limiting...
Abstract Tumors with the help of surrounding environment facilitate immune suppression in patients, and immunotherapy can counteract this inhibition. Among immunotherapeutic strategies, immunostimulatory cytokine IL-15 could represent a serious candidate for reactivation antitumor immunity. However, exogenous may have limited impact on patients cancer due to its dependency IL-15Rα frequently downregulated patients. In work, we studied activity superagonist receptor-linker–IL-15 (RLI),...