Etude structurale et serologique du mycoside A produit par Mycobacterium kansasii

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Immunothérapie anti-cancéreuse et lymphocytes T-Vgamma9Vdelta2 (stratégies contre l'échappement tumoral)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Optimisation de l'activité anti-tumorale des lymphocytes T gamma9delta 2 humains

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Single-cell differentiation trajectories define early stages of a human cutaneous T-cell lymphoma

International audienceAim: The aim of this article is to characterize in detail the γδ T lymphocytes from an adult patient with primary cutaneous T-cell lymphoma of γδ subtype (γδ CTCL). Methods: Here this article reports trajectory mapping on high-resolution differentiation trajectories of γδ T lymphocytes digitally extracted from a scRNAseq dataset. Results: In the patch-to-plaque progression of CTCL, the TCRVγnon9 subset of γδ T cells differentiated from naive T cells (Tn) and central memory T cells (Tcm) to abundant effector memory T cells (Tem) while other cutaneous γδ T and CD8 T cells remained unchanged. Conclusions: This transcriptomic switch underlies the emergence of a CTCL-like progression of the TCRVγnon9 γδ T subtype and suggests new routes for treating these diseases

Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease

International audienceThe detailed characterization of human γδ T lymphocytes at the single-cell transcriptomic level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ T lymphocytes from (n=95) patients with cancer or adult and pediatric COVID-19 disease. We found that cancer patients with human papillomavirus-positive head and neck squamous cell carcinoma and Epstein-Barr virus-positive Hodgkin’s lymphoma have γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ T lymphocytes relocalize from peripheral blood mononuclear cells (PBMC) to the infected lung tissue, where their advanced differentiation, tissue residency, and exhaustion reflect T cell activation. Although severe COVID-19 increases both recruitment and exhaustion of γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with COVID-19 display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ T cells from children with the COVID-19-related multi-system inflammatory syndrome are not lymphodepleted, but they are differentiated as in healthy PBMC. These findings suggest that some virus-induced memory γδ T lymphocytes durably persist in the blood of adults, and could subsequently infiltrate and recirculate in tumors

Poly(phosphorhydrazone) dendrimers: Yin and yang of monocyte activation for human NK cell amplification applied to immunotherapy against multiple myeloma

International audienceHuman natural killer (NK) cells play a key role in anti-cancer and anti-viral immunity, but their selective amplification in vitro is extremely tedious to achieve and remains one of the most challenging problems to solve for efficient NK cell-based immuno-therapeutic treatments against malignant diseases. Here we report that, when added to ex vivo culture of peripheral blood mononuclear cells from healthy volunteers or from cancer patients with multiple myeloma, poly (phosphorhydrazone) dendrimers capped with amino-bis(methylene phosphonate) end groups enable the efficient proliferation of NK cells with anti-cancer cytotoxicity in vivo. We also show that the amplification of the NK population relies on the preliminary activation of monocytes in the framework of a multistep cross-talk between monocytes and NK cells before the proliferation thereof. Thus poly(phosphorhydrazone) dendrimers represent a novel class of extremely promising drugs to develop NK-cell based anti-cancer therapies

Longitudinal CITE-Seq profiling of chronic lymphocytic leukemia during ibrutinib treatment: evolution of leukemic and immune cells at relapse

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A Phosphorus-Based Dendrimer Targets Inflammation and Osteoclastogenesis in Experimental Arthritis

Comment in Experimental arthritis: Dendrimer drug mends monocytes. [Nat Rev Rheumatol. 2011]International audienceDendrimers are highly branched "tree-like" polymers that have demonstrated therapeutic potential in drug delivery, medical imaging, and tissue engineering in recent years. In addition, we have shown that an azabisphosphonate (ABP)-capped dendrimer selectively targets monocytes and directs them toward anti-inflammatory activation. We explored this property to assess the therapeutic potential of dendrimer ABP in the treatment of an inflammatory disease, rheumatoid arthritis. Intravenous injections of dendrimer ABP inhibited the development of inflammatory arthritis in two animal models: IL-1ra(-/-) mice and mice undergoing K/BxN serum transfer. Suppression of disease was characterized by normal synovial membranes, reduced levels of inflammatory cytokines, and the absence of cartilage destruction and bone erosion. Dendrimer ABP also exhibited anti-osteoclastic activity on mouse and human cells, mediated by c-FMS (cellular-feline McDonough strain sarcoma virus oncogene homolog) inhibition. These preclinical demonstrations suggest the potential use of dendrimer ABP as a nanotherapeutic for rheumatoid arthritis

Evidence for Early Infection of Nonneoplastic Natural Killer Cells by Epstein-Barr Virus

We examined lymph nodes and tonsils from patients with infectious mononucleosis by combined detection of EBV-encoded RNA and a specific marker of natural killer (NK) cells, PEN5. A small number of Epstein-Barr virus (EBV) latently infected nonneoplastic NK cells were detected. Our data demonstrate that NK cells are natural targets of EBV and that infection of these cells is an early event observed during primary EBV infection