Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue, Wenhua; Yan, Dan; Kan, Quancheng

Despite that IL-35 remains a culprit in cancer therapeutics yet it plays an important regulator role in many autoimmune diseases. IL-35 is expectedly credited as therapeutic option for autoimmune diseases and pro-inflammatory states due to its antiinflammatory effects, suppression of T cells and proliferation of Treg cells. Beneficial effects of IL-35 are described in atherosclerosis [110, 111] , allergic airways disease [112] [113] [114] , and smoke-induced lung inflammation [115] . Likewise decreased level of IL-35 has been correlated with patients suffering from stable angina pectoris, unstable angina pectoris, and acute myocardial infarction [116] . Ectopic expression of IL-35 in pancreatic β cells prevents development of diabetes mellitus in NOD mice. Bettini et al. found that IL-35 expression protects animals from autoimmune diabetes via curbing T-cell infiltration and proliferation [117] . Similarly, intraperitoneal injection of rIL-35 has showed to decrease the incidence, intensity and progression of collagen-induced arthritis (CIA). Yuejun Liu et al. described that IL-35 can reduce acute graft-versus-host disease (aGVHD) by expanding Tregs and repressing Th1 responses [118] . EBI3 -/mice have confirmed the antiinflammatory properties of IL-35 in various diseases. For instance, Corona virus-induced encephalomyelitis and experimental autoimmune encephalomyelitis (EAE) were worsened in EBI3 -/mice [119] . Controversial reports have been observed regarding IL-35 role in rheumatoid arthritis [120] [121] [122] [123] . In addition, raised liver inflammation in induced liver fibrosis in IL-12p35-/-mice has been observed by Tsuda et al. [124] . The detailed review about possible role of IL-12 family including IL-35 in inflammation, autoimmune disease and infections can be read elsewhere [125, 126] .