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Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. However, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. We show that bacteria-induced colon cancer is accompanied by differential accumulation of IL-17(+)IL-22(+) colonic innate lymphoid cells (cILCs), which are phenotypically distinct from LTi and NK-22 cells, and that their depletion in mice with dysplastic inflammation blocks the development of invasive colon cancer. Analysis of the functional role of distinct Type 17 cytokines shows that although blockade of IL-17 inhibits some parameters of intestinal inflammation, reduction in dysplasia and colorectal cancer (CRC) requires neutralization of IL-22 indicating a unique role for IL-22 in the maintenance of cancer in this model. Mechanistic analyses showed that IL-22 selectively acts on epithelial cells to induce Stat3 phosphorylation and proliferation. Importantly, we could detect IL-22(+)CD3(+) and IL-22(+)CD3(−) cells in human CRC. Our results describe a new activity of IL-22 in the colon as a nonredundant mediator of the inflammatory cascade required for perpetuation of CRC, highlighting the IL-22 axis as a novel therapeutic target in colon cancer.

Original publication




Journal article


J Exp Med

Publication Date





917 - 931


Animals, Antigens, Ly, CD4 Antigens, Cell Lineage, Cell Transformation, Neoplastic, Colitis, Colon, Colonic Neoplasms, Disease Models, Animal, Disease Progression, Epithelial Cells, Gene Expression Regulation, Neoplastic, Helicobacter, Humans, Interleukins, Lymphocytes, Mice, Natural Cytotoxicity Triggering Receptor 1, Phosphorylation, STAT3 Transcription Factor