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Rôle pronostique des infiltrats lymphocytaires T CD4 dans les cancers du sein

Abstract : Tumor escape to immune system surveillance is one of the reasons why human cancer achieves to grow. In my research team, we aim to study CD4 T cell populations and their functions in the context of cancer. My work was precisely to determine if the results obtained in mice could be transposable in humans, in the context of breast cancer. . We first unraveled that tumor infiltrating Th17 cells could inhibit effector and cytotoxic functions of Th1 and CD8 T cells in an ectonucleotidase-dependent manner. Finally, we showed that high tumor infiltration in IL-17+ cells were significantly associated with a worse clinical prognosis for breast cancer patients. Then, we aim to prevent Th17 cell differentiation. We first established that SIRT1 activation reduces STAT3 acetylation thus limiting Th17 cell differentiation. Activation of SIRT1 limits in vivo Th17 cell expansion and leads to the decrease of tumor growth. This concept has been validated in humans and gives the possibility to associate SIRT1 agonists with chemotherapy. The last project concerns the role and the prognosis impact of Th9 lymphocytes in breast cancer. We highlighted that the effector properties of human Th9 cells could be increased by IFNα via IRF1 activation. Finally, we attested that the tumor infiltration of Th9 lymphocytes was associated with a better prognosis for breast cancer patients.
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Submitted on : Friday, June 28, 2019 - 1:03:09 AM
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  • HAL Id : tel-02167634, version 1



Marion Thibaudin. Rôle pronostique des infiltrats lymphocytaires T CD4 dans les cancers du sein. Santé. Université Bourgogne Franche-Comté, 2017. Français. ⟨NNT : 2017UBFCI014⟩. ⟨tel-02167634⟩



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