Linking inflammation to colon cancer: a novel role for interleukin(IL)-22⁺ innate lymphoid cells

▸ Kirchberger S, Royston DJ, Boulard O, et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med 2013;210:917-30.1

Bacteria-induced inflammatory pathways are key drivers of carcinogenesis in malignancies such as Helicobacter pylori-induced gastric cancer and colitis-associated cancer (CAC). Patients with inflammatory bowel disease have an increased risk of colon cancer due to aberrant inflammatory responses toward the intestinal microbiota; however, the immune mediators that are involved in the transition from colitis to colon cancer are unclear. IL-22 is important in TH17 responses and has both protective and detrimental properties in colitis, but not much is known about its role in colorectal cancer (CRC). In addition to TH17 cells, IL-22 can be produced by RORγt-expressing innate lymphoid cells (ILCs). Colonic ILCs (cILCs), together with LTi cells and NK-22 cells, are members of the newly defined ROR-γt⁺ ILCs, which contribute to host defense and inflammation. In this study Kirchberger and colleagues set out to examine the role of ILC and Type 17 cytokines in the development and maintenance of bacteria-driven CAC. An innate model in which genetically susceptible mice are infected with Helicobacter hepaticus (Hh) and treated with the carcinogen azoxymethane to develop CAC was used throughout the study. The authors found that IL-17⁺IL-22⁺ cILCs, which are phenotypically different than LTi and NK-22 cells, accumulate during cancer development. These cILCs were necessary for the transition from established chronic inflammation to colon cancer. Functional analysis of cILC-associated cytokines showed that IL-17 and IL-22 seemed to have distinct functional roles in inflammation and tumour development, because blocking only IL-22 ameliorated established colitis and reduced tumour burden. Mechanistic analyses to determine how IL-22 maintains inflammation and cancer indicated that IL-22 regulates epithelial proliferation, myeloid cell recruitment, and antimicrobial defense. Notably, the …