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Mise en évidence et étude d'une isoforme alternative du facteur de transcription IRF-1 dans la différenciation lymphocytaire Th1

Abstract : It is now clearly established that immune system can affect cancer response to therapy. However, the influence of tumor microenvironment on immune cells is not completely understood. In this respect, alternative splicing is increasingly described to affect immune system biology.Here, we showed that tumor microenvironment, by increasing alternative splicing events, induced the expression of an alternative isoform of the IRF1 transcription factor in Th1 cells. Furthermore, we also showed, in both mice and humans, that IRF1 alternative isoform alters IRF1 full form transcriptional activity on Il12rb1 promotor, resulting in decreased IFN-γ secretion in Th1 cells.Thus, the expression of the IRF1-short isoform increases in tumor microenvironment. Prevent this isoform appearance could potentiate Th1 cell antitumor effect.
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Antoine Bernard. Mise en évidence et étude d'une isoforme alternative du facteur de transcription IRF-1 dans la différenciation lymphocytaire Th1. Médecine humaine et pathologie. Université Bourgogne Franche-Comté, 2019. Français. ⟨NNT : 2019UBFCI014⟩. ⟨tel-02502728⟩

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