Interleukin-22 (IL-22) is an
IL-10 family
cytokine produced by T cells and innate lymphoid cells. The
IL-22 signaling pathway orchestrates mucosal immune defense and tissue regeneration through pleiotropic effects including pro-survival signaling, cell migration, dysplasia and angiogenesis. While these functions can prevent initial establishment of
tumors, they can also be hijacked by aggressive
cancers to enhance
tumor growth and
metastasis. Thus, the role of the IL-22/IL-22R1 axis in
cancer is complex and context-specific. Evidence of
IL-22 involvement manifests as dysregulation of
IL-22 expression and signaling in patients with many common
cancers including those of the gut, skin, lung and liver. Unlike other
cancer-associated
cytokines,
IL-22 has restricted tissue specificity as its unique receptor
IL-22R1 is exclusively expressed on epithelial and tissue cells, but not immune cells. This makes it an attractive target for
therapy as there is potential achieve anti-
tumor immunity with fewer side effects. This review summarizes current findings on functions of
IL-22 in association with general mechanisms for
tumorigenesis as well as specific contributions to particular
cancers, and ponders how best to approach further research in the field.