| Literature DB >> 33419764 |
Frédérique Végran1,2,3, Romain Boidot1,2,3,4, Antoine Bernard5,2,3, Christophe Hibos5,2, Corentin Richard2,3, Etienne Viltard5,2, Sandy Chevrier3, Sophie Lemoine6, Joséphine Melin2,7, Etienne Humblin5,2, Romain Mary5,2, Théo Accogli5,2, Fanny Chalmin5, Mélanie Bruchard5,2,3, Paul Peixoto8, Eric Hervouet8, Lionel Apetoh5,2, François Ghiringhelli5,2,3.
Abstract
It is clearly established that the immune system can affect cancer response to therapy. However, the influence of the tumor microenvironment (TME) on immune cells is not completely understood. In this respect, alternative splicing is increasingly described to affect the immune system. Here, we showed that the TME, via a TGFβ-dependent mechanism, increased alternative splicing events and induced the expression of an alternative isoform of the IRF1 transcription factor (IRF1Δ7) in Th1 cells. We found that the SFPQ splicing factor (splicing factor, proline- and glutamine-rich) was responsible for the IRF1Δ7 production. We also showed, in both mice and humans, that the IRF1 alternative isoform altered the full-length IRF1 transcriptional activity on the Il12rb1 promoter, resulting in decreased IFNγ secretion in Th1 cells. Thus, the IRF1Δ7 isoform was increased in the TME, and inhibiting IRF1Δ7 expression could potentiate Th1 antitumor responses. ©2021 American Association for Cancer Research.Entities:
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Year: 2021 PMID： 33419764 DOI： 10.1158/2326-6066.CIR-19-0679
Source DB: PubMed Journal: Cancer Immunol Res ISSN： 2326-6066 Impact factor: 11.151