CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

It has become evident that bacteria in our gut affect health and disease, but less is known about how they do this. Recent studies in mice showed that gut Clostridium bacteria and their metabolites can activate regulatory T cells (Treg) that in turn mediate tolerance to signals that would ordinarily cause inflammation. In this study we identify a subset of human T lymphocytes, designated CD4CD8αα T cells that are present in the surface lining of the colon and in the blood. We demonstrate Treg activity and show these cells to be activated by microbiota; we identify F. prausnitzii, a core Clostridium strain of the human gut microbiota, as a major inducer of these Treg cells. Interestingly, there are fewer F. prausnitzii in individuals suffering from inflammatory bowel disease (IBD), and accordingly the CD4CD8αα T cells are decreased in the blood and gut of patients with IBD. We argue that CD4CD8αα colonic Treg probably help control or prevent IBD. These data open the road to new diagnostic and therapeutic strategies for the management of IBD and provide new tools to address the impact of the intestinal microbiota on the human immune system

Thérapie cellulaire T adoptive

International audienc

PD-1 expression on tumor-specific T cells: Friend or foe for immunotherapy?

International audienc

Adoptive transfer with high-affinity TCR to treat human solid tumors: how to improve the feasibility?

International audienceThe adoptive transfer of tumor antigen-specific T cells recently achieved clinical efficacy for a fraction of melanoma patients refractory to other therapies. Unfortunately , the application of this strategy to the remaining melanoma and most other cancer patients is hampered by the difficulty to generate high-affinity tumor-reactive T cells. Two strategies are currently developed to extend the feasibility of this therapeutic approach: clinical grade tool production for MHC-peptide multimer-driven sorting of antigen-specific T cells from the endogenous peripheral T cell repertoire and de novo engineering of the missing repertoire by genetic transfer of cloned specific T cell receptor (TCR) into T cells. The expected multiplication of adoptive transfer treatments, by these strategies, and their careful evaluation should enable the cure of a number of otherwise compromised cancer patients and to gain insight into the characteristics of transferred T cells best fitted to eradicate tumor cells, in terms of antigen specificities, phenotype, and functions. In particular, identification of tumor-rejection antigens by this approach would improve the design and efficacy of all immuno-therapeutic approaches

Lymphocyte Biomarkers of Clinical Responses to Adoptive Immunotherapy of Malignant Melanoma

International audienceDuring the last few years, adoptive cellular therapy (ACT)-the isolation of antigen-specific lymphocytes, their ex vivo expansion and activation, and subsequent autologous administration-has been tested for treatment of melanoma tumours. Initial ACT used melanoma-infiltrating lymphocytes (TIL) that often contain tumour reactive lym-phocytes, of diverse, mostly unknown, specificities [1, 2]. Recently, the identification of melanoma antigens [3] and the development of techniques for selection and expansion of epitope specific T cells has opened the way to the use of tumour antigen specific T cells, and importantly to immune follow up of ACT [4-9]. Despite these advances, several issues remain to address to achieve the major aims of ACT, as the rapid production of clinical grade T cells capable of eliciting a significant destruction of tumour tissue

ROLE OF miRNA FROM MELANOMA CELL-DERIVED EXOSOMES IN TUMOR IMMUNE ESCAPE

International audienc

Conference Scenes: Immunotherapies in transplantation and cancer

International audienceThis 22th edition of the NAT (« Nantes Actualités Transplantation ») annual meeting was co-organized for the second time with the LabEx IGO network (« Immuno-Graft Oncology »). This international meeting was held on 1 and 2 June 2017 in Nantes (Western of France). The topic of this 2-days meeting was “Immunotherapies in transplantation and cancer”. This meeting brought together 17 international invited speakers, young researchers and 220 attendees mainly from Europe and North America. It was a unique opportunity to bring together the pioneers and leading immunologists in the fields of transplantation and cancer, focusing on shared mechanisms that control immune responses in organ or bone marrow transplantation and in cancer

Is antigen specificity the key to efficient adoptive T‑cell therapy?

International audienceAdoptive transfer of T cells remains a promising approach in melanoma. Initial clinical trials performed with polyclonal tumor-infiltrating lymphocyte gave limited clinical results. Nonetheless, encouraging results have been reported in adjuvant setting (stage III melanoma), and when tumor-infiltrating lymphocytes were associated with lymphodepleting regimens. Specificity of adoptive cell therapy has been achieved with the infusion of antigen specific cytotoxic T-lymphocyte clones, associated with some clinical responses. Antigen specificity can also be obtained by the allogeneic transfer of high-avidity T-cell receptors into autologous T cells. We propose an alternative strategy based on the selection of antigen-specific T cells with magnetic beads coated with HLA-peptide multimers. Future improvements of adoptive melanoma immunotherapy may be achieved by its association with other therapeutic strategies such as targeted therapy against signaling pathways