A5073834546- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Ocular Oncology and Treatments
- Advanced biosensing and bioanalysis techniques
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Nanoplatforms for cancer theranostics
- CAR-T cell therapy research
- Trypanosoma species research and implications
- Immune cells in cancer
- Research on Leishmaniasis Studies
- Psoriasis: Treatment and Pathogenesis
- Adenosine and Purinergic Signaling
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- T-cell and Retrovirus Studies
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Calcium signaling and nucleotide metabolism
- Galectins and Cancer Biology
- Rheumatoid Arthritis Research and Therapies
- Innovative Microfluidic and Catalytic Techniques Innovation
- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- Liver Diseases and Immunity
Université Paris Sciences et Lettres
2018-2024
Inserm
2018-2024
Institut Curie
2018-2024
Immunité et Cancer
2023-2024
Universidad Nacional de Córdoba
2012-2022
Consejo Nacional de Investigaciones Científicas y Técnicas
2016-2022
Research Centre in Biological Chemistry of Córdoba
2018-2021
The ability of CD8+ T lymphocytes to eliminate tumors is limited by their engender an immunosuppressive microenvironment. Here we describe a subset tumor-infiltrating cells marked high expression the ATP ecto-nucleotidase CD39. frequency CD39highCD8+ increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD39 exhibited features exhaustion, such as reduced production TNF and IL2 coinhibitory receptors. Exhausted CD39+CD8+ from mice hydrolyzed extracellular ATP,...
Abstract Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated local immunosuppression, which can be partly mediated regulatory T (Tregs). Here, we study Tregs from matched tumor-invaded non-invaded TDLNs, tumors. We observe that Treg frequencies increase nodal invasion, express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while show conserved suppressive function TDLN tumor,...
Members of the IL-17 cytokine family play an important role in protection against pathogens through induction different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during acute phase T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate IL-17RA, common receptor subunit for many members, is required host resistance Furthermore, infected KO mice lack response to several cytokines showed amplified inflammatory responses with exuberant IFN-γ TNF...
Disruption of splicing patterns due to mutations genes coding factors in tumors represents a potential source tumor neoantigens, which would be both public (shared between patients) and tumor-specific (not expressed normal tissues). In this study, we show that the factor SF3B1 uveal melanoma generate such immunogenic neoantigens. Memory CD8+ T cells specific for these neoantigens are preferentially found 20% patients with bearing SF3B1-mutated tumors. Single-cell analyses neoepitope-specific...
Abstract Regulatory T cells (Tregs) are plastic playing a pivotal role in the maintenance of immune homeostasis. Tregs actively adapt to microenvironment where they reside; as consequence, their molecular and functional profiles differ among tissues pathologies. In tumors, features acquired by remains poorly characterized. Here, we observe that human tumor-infiltrating selectively overexpress CD74, MHC class II invariant chain. CD74 has been previously described regulator antigen-presenting...
Although CD8+ T cells undergo autonomous clonal proliferation after antigen stimulation in vivo, the expansion of activated CD4+ is limited by intrinsic factors that are poorly characterized. Using genome-wide CRISPR-Cas9 screens and an vivo system modeling antigen-experienced cell recruitment during a localized immune response, we identified suppressor cytokine signaling 1 (SOCS1) as major nonredundant checkpoint imposing brake on proliferation. anti–interleukin-2 receptor (IL-2R) blocking...
There is a compelling need for approaches to predict the efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics generate 3D cell co-cultures embedded in hydrogels that recapitulate simplified tumor ecosystems. Here, we present development and validation lung tumor-on-chip platforms quickly precisely measure ex vivo effects immune checkpoint inhibitors on T cell-mediated cancer death by exploiting power live imaging advanced image analysis algorithms. The integration...
Abstract Effective antibody responses are essential to generate protective humoral immunity. Different inflammatory signals polarize T cells towards appropriate effector phenotypes during an infection or immunization. Th1 and Th2 have been associated with the polarization of responses. However, follicular helper (Tfh) a unique ability access B cell follicle support germinal center (GC) by providing help. We investigated specialization Tfh induced under type-1 type-2 conditions. first studied...
The IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood. CD8+ T lymphocytes key elements microbes, and their survival ability mount cytotoxic responses orchestrated several cytokines. Here, we demonstrated IL-17RA-signaling cytokines sustain pathogen-specific cell immunity. absence of IL-17RA IL-17A/F during Trypanosoma cruzi infection resulted in increased tissue parasitism reduced frequency parasite-specific cells....
Senescent T cells have been described during aging, chronic infections, and cancer; however, a comprehensive study of the phenotype, function, transcriptional program this cell population in breast cancer (BC) patients is missing. Compared to healthy donors (HDs), BC exhibit an accumulation KLRG-1+CD57+ CD4+ CD8+ peripheral blood. These infiltrate tumors tumor-draining lymph nodes. from HDs features senescence, despite their inhibitory receptor expression, they produce more effector...
Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary (PBC) are chronic diseases in which cholangiocytes primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA almost never found autoimmune context PBC. Here, we hypothesized that PBC might favor immunosurveillance. In preclinical murine models challenged with syngeneic (but not PSC) reduced frequency development delayed...
Abstract Solid tumors are infiltrated by immune cells where macrophages and senescent T highly represented. Within the tumor microenvironment, a cross-talk between infiltrating may occur conditioning characteristic of in situ response. Our previous work showed that induce senescence cells, which powerful suppressors lympho-proliferation. In this study, we report Tumor-Induced Senescent (TIS)-T also modulate monocyte activation. To gain insight into interaction, CD4+ or CD8+TIS-T control-T...
IL-17 immune responses in cancer are controversial, with both tumor-promoting and tumor-repressing effects observed. To clarify the role of signaling progression, we used syngeneic tumor models from different tissue origins. We found that deficiencies host IL-17RA or IL-17A/F expression had varying on
Abstract Germinal centers (GC) are important sites for high-affinity and long-lived antibody induction. Tight regulation of GC responses is critical maintaining self-tolerance. Here, we show that Galectin-3 (Gal-3) involved in development. Compared with WT mice, Gal-3 KO mice have more B cells T follicular helper cells, increased percentages antibody-secreting higher concentrations immunoglobulins IFN-γ serum, develop a lupus-like disease. blockade reduces spontaneous formation, class-switch...
Conventional CD4+ T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to elimination remains poorly understood. Here, we describe a subset of tumor-infiltrating Tconv cells characterized by the expression CD39. In several mouse cancer models, observed that CD39+ accumulated tumors but were absent lymphoid organs. Compared CD39- counterparts, exhibited cytotoxic and exhausted signature at transcriptomic level, confirmed high protein inhibitory receptors...
While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, regulatory response mediated by Treg upon infection Trypanosoma cruzi was still poorly characterized. In order to understand role during this protozoan parasite, we determined in time space magnitude phenotypic, functional transcriptional features cell population infected mice. Contrary accumulation reported most...
Monoclonal antibody targeting the CD20 antigen on B cells is used to treat majority of non-Hodgkin lymphoma patients and some autoimmune disorders. This therapy generates adverse effects, notably opportunistic infections activation viruses from latency. Here, using infection murine model with intracellular parasite Trypanosoma cruzi , we report that anti-CD20 treatment affects not only cell responses but also CD8 + T responses, representing most important immune effectors involved in control...
Innate CD8+ T cells express a memory-like phenotype and demonstrate strong cytotoxic capacity that is critical during the early phase of host response to certain bacterial viral infections. These arise in thymus depend on IL-4 IL-15 for their development. Even though innate exist WT mice low numbers, they are highly enriched KO lack kinases, leading an increase production by thymic NKT cells. Our work describes C57BL/6 undergoing Th1 biased infectious disease, experiences enrichment single...
Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern migration of infected people. It been reported that persistence as well intensity inflammatory immune response are determinants clinical manifestations disease. Even though inflammation indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report importance B cells conditioning T cell T. cruzi...
Objective Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis ( RA ) were correlated activation, disease activity, response to treatment, as well receptor–mediated pathways functional. Methods Using flow cytometry, we performed extensive phenotypic functional evaluation CD 4+ 8+ blood synovial fluid SF ex...