Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue, Wenhua; Yan, Dan; Kan, Quancheng

IL-35 signaling is also reported to cause the suppression of immune cells-led anti-tumor activities in TME thorough inhibiting the Th17 cells growth [50, 101] . The exact role of Th17 in cancer development remains a controversial subject itself due to Th17 cells plasticity. Both pro-inflammatory and anti-inflammatory effects of Th17 are put forward, but number of studies in relation to IL-35 is not enough to be conclusive. For example, one study manifests Th17 as pro-tumor attributed largely to the secretion of IL-17 [102, 103] , while other exerts anti-tumor actions by promoting immune cells into tumors, activating effector CD8(+) T cells, or directly through converting toward Th1 phenotype and producing IFN-γ [104] . Although IL-35 inhibits the Th17 cells [38] , but it is premature to jump to conclusion that it can also play a role in cancer immunity as Th17 cells inhibition can also lead to the suppression of its anti-tumor action via different mechanism described above. Therefore it may be plausible to say that IL-35 induced Th-17 inhibition inconclusively and/or partially suppresses the anti-tumor activities.