Interleukin 35: New Target for Immunotherapy Targeting the Tumor Microenvironment.

Interleukin 35 (IL-35) is a newly discovered inhibitory cytokine of the interleukin 12 family. More recently, IL-35 was found to be increased in the tumor microenvironment (TME) and peripheral blood of many cancer patients, indicating that it plays an important role in TME. Tumors secrete cytokines that recruit myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg) into the TME to promote malignant progression which is a great challenge for cancer treatment. Radiotherapy causes serious adverse effects, and tumor resistance to immune checkpoint inhibitors is still an unsolved challenge.New cancer therapy approaches are urgently needed. Numerous studies have shown that IL-35 can recruit immunosuppressive cells to enable tumor immune escape by promoting the conversion of immune cells into a tumor growth-promoting phenotype as well as facilitating tumor angiogenesis. IL-35-neutralizing antibodies were found to boost the chemotherapeutic effect of gemcitabine and considerably reduce the microvascular density. Therefore, targeting IL-35 in the TME provides a promising cancer treatment target. In addition, IL-35 may be used as an independent prognostic factor for some tumors in the near future. This review intends to reveal the interplay of IL-35 with immune cells in the tumor microenvironment, which may provide new options for cancer treatment.