The Emerging Role of the IL-17B/IL-17RB Pathway in Cancer

Among inflammatory mediators, a growing body of evidence emphasizes the contribution of the interleukin 17 (IL-17) cytokine family in malignant diseases. Besides IL-17A, the prototypic member of the IL-17 family, several experimental findings strongly support the role of the IL-17B/IL-17 Receptor B (IL-17RB) pathway in tumorigenesis and resistance to Anticancer therapies. In mouse models, IL-17B signaling through IL-17RB directly promotes Cancer cell survival, proliferation, and migration, and induces resistance to conventional chemotherapeutic agents. Importantly, recent work by our and other laboratories showed that IL-17B signaling dramatically alters the tumor microenvironment by promoting chemokine and cytokine secretion which foster tumor progression. Moreover, the finding that elevated IL-17B is associated with poor prognosis in patients with pancreatic, gastric, lung, and breast Cancer strengthens the results obtained in pre-clinical studies and highlights its clinical relevance. Here, we review the current understanding on the IL-17B/IL-17RB expression patterns and biological activities in Cancer and highlight issues that remain to be addressed to better characterize IL-17B and its receptor as potential targets for enhancing the effectiveness of the existing Cancer therapies.

IL-17; IL-17B; IL-17RB; cancer; cancer therapy; inflammation.