Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue, Wenhua; Yan, Dan; Kan, Quancheng

There are some contradictory results as well, pressing the point that IL-35 does not act in a same way in all types of cancer and hence its role can be unique in different kind of immune situations. For example it was shown that IL-35 might have inhibitory actions in colon cancer growth. Not only was the expression of IL-35 in colon cancer low but the anti-tumor effects of IL-35 on colon cancer cell lines also appeared in a dose dependent manner [105] . It was found that mechanistically the inhibition of β-catenin is involved in the IL-35 induced blunting action on colon cancer. Authors indicated that the reason for these contradictory results are unclear and requires further investigation. Such paradoxical results are also endorsed by Jun Long et al. in one clinical study which revealed the data form 75 Hepatocellular carcinoma (HCC) patients. IL-35 expression in advance stages of HCC was lowered as compared to early stages of the disease. The expression of IL-35 changed inversely as the key feature of HCC e.g. tumor size, microvascular invasion, and histological grades advanced [106] . Conversely, Fu et al. highlighted that overexpression of IL-35 is correlated with the HCC aggressiveness [107] . Correspondingly, the effects of IL-35 in inhibiting cancer development, curtailing tumor growth and inducing the apoptosis in human cancer cells were reported by Long et al. in 2013 [23] .