Anti-cancer versus cancer-promoting effects of the interleukin-17-producing T helper cells

Research on T helper 17 (Th17) cells with regard to immunoediting has revealed elusive results. Whereas enhanced Th17 response and related molecules such as interleukin (IL)-17, IL-21, IL-22, IL-23 and STAT3 accompanied tumor induction and progression, finding that tumor growth/stage was negatively correlated with increased infiltration of Th17 cells in the tumor mass has prompted elucidation of various antitumor mechanisms elicited by Th17 and their related molecules. The pro-tumor efficacy of Th17 response included promotion of neutrophilia and induction of angiogenic (e.g. VEGF, MMP2 and MMP9) and anti-apoptotic factors (e.g. Bcl-XL), as well as expansion and activation of myeloid-derived suppressor cells, which facilitate generation of tumor-specific regulatory T cells. Other tumor immunogenic settings revealed anti-tumor pathways including induction of cytotoxic activity, expression of MHC antigens, the ability Th17 cells to reside within the tumor, and to convert into IFN-γ producers. Notably, Th17 cell related molecules exert indirect pro- or anti-tumor effects via inducing viral persistence or mediating protective mechanisms against bacterial and viral infection. Herein, the recent literature revealing such immunoediting events mediated by Th17 cells and their associated molecules as delivered by various experimental regimens and observed in cancer patient are revised, with a focus on some proposed anti-cancer therapies.

► IL-17 producing cells are implicated in mediating pro- and anti-tumor events in various tumor models and cancer patients.
► The pro-tumor events include induction of angiogenic and anti-apoptotic factors, migration, invasion and generation of MDSCs.
► Th17 cells mediate anti-tumor mechanisms by promoting CTLs activities, MHC antigen expression, and production of IFN-γ.
► Targeting Th17 molecules should consider their impacts in mediating autoimmune manifestation and anti-microbial responses.