Plasticity Of Th17 Cells Are Regulated By The Cross Talk With Tumor Cells

Different subsets of T cells which are differentiated by Stimulation of antigens and particularcytokine signals, perform distinct functions contrary to their identical origin; TCD4+ precursors. Thelper 17 (Th17) cells are characterized by high production of IL-17 and inflammatory cytokines,considered as crucial cells to induce inflammation and also indicated as a clue in pathogenesis ofmany autoimmune diseases and allergy reactions. The role of Th17 in tumor immunity has beenremained controversial. Therefore, in this review we aimed to clarify the role of Th17 in tumorpromotion or suppression.Recently some data demonstrated that high percentage of Th17 cellsinfiltrated to tumor site, more than other tumor infiltrating lymphocytes (TILs). Under normalconditions IL-6 with TGF-β induce Th17 and inhibit Treg differentiation. This proved that IL-6 is acritical factor to create a balance between Th17/Treg differentiation. Moreover, Th17 is able toconvert into Th1, Th2 and Treg based on cross talk with tumor microenvironment and to exhibitboth anti-tumor and pro-tumor activity. IL-17 production by Th17 cells might lead to angiogenesisand recruitment of myeloid-derived suppressor cells (MDSCs). Furthermore, TGF-β in tumormicroenvironment might induce differentiation of Th17 into Treg by induction of ectonucleotidasesexpression. Although, tumor cells and tumor associated fibroblast cells are able to provide cell-cellcontact in addition to secret pro-inflammatory cytokines, which cause to Th17 cells expansion. Th17cells were shown to inhibit tumor growth by induction of effector cells recruitment in tumor and byactivation of tumor-specific T CD8+ cells. As well as, plasticity might add more functions to Th17cells in tumor immunity. Whether Th17 conversion to Treg cells requires further confirmation, butmight cause to immunosuppression features in Th17 cells. On the opposite side, Th17 cells mightconvert to Th1 cells phenotype and produce IFN-γ and TNF-α in the tumor site which in turn couldlead to tumor growth inhibition. Tumor microenvironment with infiltrated cells such as Fibroblast,immune cells and mesenchymal stem cells provide milieu can affect on th17 plasticity. Moreover,Th17 plays dual role in tumor site, promoting or suppressing based on crosstalk with tumormicroenvironment.