Targeting the IL-9 pathway in cancer immunotherapy

Interleukin (IL)-9 is a pleiotropic cytokine, which can function as a positive or negative regulator of immune responses on multiple types of cells. The role of IL-9 was originally known in allergic disease and parasite infections. Interestingly, recent studies demonstrate its presence in the tumor tissues of mice and humans, and the association between IL-9 and tumor progression has been revisited following the discovery of T helper (Th) 9 cells. Tumor-specific Th9 cells are considered to be the main subset of CD4(+) T cells that produce high level of IL-9 and exhibit an IL-9-dependent robust anti-cancer function in solid tumors. IL-9 exerts an unprecedented anti-tumor immunity not only by inducing innate and adaptive immune responses but also directly promoting apoptosis of tumor cells. The objective of this review is to summarize the latest advances regarding the anti-tumor mechanisms of IL-9 and Th9 cells.