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_H17) 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_H17 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.

大约 25% 的癌症发生在肿瘤发生部位的慢性炎症之前。然而，这种通常发生在肠道中的多因素致癌过程是否可以由特定的免疫细胞群启动尚不清楚。在这里，我们发现，源自产生白细胞介素 17 (IL-17) 的辅助 T (T _H 17) 细胞的肠道 T 细胞亚群可诱导肠上皮的自发转化。该亚群产生炎症细胞因子，其致瘤潜力不依赖于 IL-17 的产生，而是依赖于转录因子 KLF6 和 T-BET 以及干扰素-γ。这种细胞类型的发育受到肠上皮细胞产生的转化生长因子-β1 (TGFβ1) 的抑制。 TGFβ 信号传导作用于致瘤前 T _H 17 细胞亚群，通过抑制 KLF6 依赖性 T-BET 表达来防止其进展至致瘤阶段。因此，这项研究确定了引发癌症的肠道 T 细胞亚群。