The Role of IL-35 in Regulating Tumor Immunity

Junfeng Zhang, Yunsheng Zhang, Chunlei Li, Xiaomei Zhang, Huabao Xiong, Hongxin Deng


Interleukin 35 (IL-35) is the newest identified heterodimeric cytokine in the IL-12 cytokine family. IL-35 is a heterodimer comprised of IL-12 subunit alpha (p35) and IL-27 subunit Epstein-Barr virus-induced gene 3 (EBI3). Since discovery, IL-35 showed different immunosuppressive functions from other members of the IL-12 family. It is shown that IL-35 inhibits immune responses by suppressing the differentiation of Th17 cells and macrophages and inhibiting the proliferation and function of effector T cells. Although studies showed that IL-35 has been secreted by regulatory T cells, CD8+ regulatory T cells and regulatory B cells, other studies have also shown that IL-35 may be more widely expressed in cancer cell lines, such as lung adenocarcinoma, hepatocellular carcinoma, cervical carcinoma, breast cancer, and gastric cancer. Recent studies have also shown that IL-35 secreted by tumor cells promotes both tumor growth and metastasis by enhancing the accumulation of angiogenesis and myeloid-derived suppressor cells, and decreasing the infiltration of CD8+ T cells into tumor microenvironment. In this review, the structure and biological functions of IL-35 were reviewed in detail, and the roles of IL-35 in different types of cancers including colorectal cancer, pancreatic ductal adenocarcinoma, acute myeloid leukemia, hepatocellular carcinoma, breast cancer and so on were discussed.


Interleukin 35; Cancer; IL-35 signaling; Microenvironment

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