An intestinal TH17 cell-derived subset can initiate cancer

Olivier Fesneau (1) , Valentin Thevin (1) , Valérie Pinet (2) , Chloe Goldsmith (1) , Baptiste Vieille (1) , Saidi Soudja (1) , Rossano Lattanzio (3) , Michael Hahne (2) , Valérie Dardalhon (2) , Hector Hernandez-Vargas (1) , Nicolas Benech (1, 4) , Julien Marie (1)

1 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
2 IGMM - Institut de Génétique Moléculaire de Montpellier
3 University "G. d'Annunzio" of Chieti-Pescara [Chieti]
4 HCL - Hospices Civils de Lyon

Abstract Approximately 25% of cancers are preceded by chronic inflammation that occurs at the site of tumor development. However, whether this multifactorial oncogenic process, which commonly occurs in the intestines, can be initiated by a specific immune cell population is unclear. Here, we show that an intestinal T cell subset, derived from interleukin-17 (IL-17)-producing helper T (T H 17) cells, induces the spontaneous transformation of the intestinal epithelium. This subset produces inflammatory cytokines, and its tumorigenic potential is not dependent on IL-17 production but on the transcription factors KLF6 and T-BET and interferon-γ. The development of this cell type is inhibited by transforming growth factor-β1 (TGFβ1) produced by intestinal epithelial cells. TGFβ signaling acts on the pretumorigenic T H 17 cell subset, preventing its progression to the tumorigenic stage by inhibiting KLF6-dependent T-BET expression. This study therefore identifies an intestinal T cell subset initiating cancer.

Domaines: Cancer

Olivier Fesneau, Valentin Thevin, Valérie Pinet, Chloe Goldsmith, Baptiste Vieille, et al.. An intestinal TH17 cell-derived subset can initiate cancer. Nature Immunology, 2024, ⟨10.1038/s41590-024-01909-7⟩. ⟨hal-04675685⟩