Targeting interleukin-22 for cancer therapy.

Interleukin-22 (IL-22) is a member of IL-10 family of cytokines. IL-22 induces proliferative and anti-apoptotic signaling pathways and production of anti-microbial molecules that enhance tissue regeneration and host defense. IL-22 has also been identified as a cancer-promoting cytokine since deregulation of the IL-22-IL-22R1 system is linked to different cancer entities including lung, breast, gastric, pancreatic and colon cancers. T cells and innate lymphoid cells are the main cellular sources of IL-22. Expression of its specific receptor IL-22R1 is restricted to the non-hematopoietic cells which makes the IL-22-IL-22R1 pathway an attractive target for anti-cancer therapy. For development of such therapies, a better understanding of IL-22 regulation in the tumor microenvironment is needed. We could recently decipher how cancer cells promote IL-22 production by memory T cells via induction of IL-1. Here we will discuss how this knowledge might contribute to developing therapies disregulating the IL-22 pathway for cancer immunotherapy.