IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation

Significance Chronic inflammatory diseases are well-recognized causes of cancer and account for up to 20% of all cancer deaths worldwide. However, the mechanism that initiates the development of a tumor-promoting immune environment in chronic inflammation is not known. Using mouse models of chronic skin and colon inflammation and human samples, we show IL-33 triggers the transition from tumor-suppressive immunity to chronic, tumor-promoting inflammation through a regulatory T cell-dependent mechanism. Our findings demonstrate a generalized dependency of tumor-promoting immune environments on the IL-33/Treg axis both in the skin and colon. Based on these findings, IL-33/Treg axis blockade may be an attractive therapeutic strategy for the treatment and prevention of cancers associated with chronic inflammatory diseases and potentiating the antitumor immunity induced by cancer immunotherapeutics.