Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue, Wenhua; Yan, Dan; Kan, Quancheng

Immune evasion plays a key role in the development and progression of cancer [46, 47] , which largely results from the failure of immune system to respond to particular tumor. This chiefly is achieved by the induction of immunosuppressive forces, which release cytokines to switch off the immune system and causes immune evasion of tumor. IL-35 is seen as critical immunosuppressive cytokine involved in immune evasion. The immune-cancer nexus is a well-established link as immune system plays a vital role in prevention, development and therapy of cancer [48] . Friedman and Liao explained that IL-35 is an important driver in cancer development as it enhances angiogenesis and blocks CD8 + T cells via releasing TGF-β [49] . One recent study has implicated IL-35 in breast cells cancer, showing greater induction of iTr35 in TME and causing inhibition of conventional T cell which subsequently converted in iTr35 [50] . Similar evidence was provided by Wang [51] was assumed and two kinds of plasmacytoma cells were injected into wild type mice. One of the type consisted of tumor cells that were transfected with IL-35 to raise the amount of IL-35 into TME while second used normal plasmacytoma cells that produced very small amount of IL-35. It was exhibited that model simulation corresponds with the experimental data shown in the experiments of Wang et al.