An intestinal TH17 cell-derived subset can initiate cancer
Olivier Fesneau, Valentin Thevin, Valérie Pinet, Chloé Goldsmith, Baptiste Vieille, Saïdi M. Soudja, Rossano Lattanzio, Michael Hahne, Valérie Dardalhon, Héctor Hernández‐Vargas, Nicolas Benech, Julien C. Marie
Abstract
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.