Abstract
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.
Highlights
The interleukin 17 (IL-17) cytokine family and its receptors play crucial roles in normal host immune responses
Our own unpublished data in mouse models suggest that IL-17B-driven alterations in the TME are the major contributors of the anticancer effect after IL-17B neutralization
As IL-17 receptor B (IL-17RB) is a common receptor for both IL-17B and IL-17E that binds to the heterodimeric complex IL-17RA and IL-17RB [19], the anticancer effect of IL-17E (IL-25) must be taken into account
Summary
The IL-17 cytokine family and its receptors play crucial roles in normal host immune responses. In mouse models, IL-17B signaling through IL-17RB promotes cancer cell survival, proliferation, and migration [9,10,11,12], while in humans, elevated IL-17B expression has been associated with poor prognosis in patients with different cancer types [10,11,12]. High expression of IL-17B or its receptor has been associated with poor patient prognosis in different cancer types (see Table 1).
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