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.

中文翻译：

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白细胞介素35：针对肿瘤微环境的免疫治疗新靶点

白细胞介素 35 (IL-35) 是白细胞介素 12 家族中新发现的抑制性细胞因子。最近，发现IL-35在许多癌症患者的肿瘤微环境（TME）和外周血中增加，表明它在TME中发挥重要作用。肿瘤分泌细胞因子，将骨髓源性抑制细胞（MDSC）和调节性T细胞（Treg）招募到TME中，促进恶性进展，这对癌症治疗来说是一个巨大的挑战。放疗会造成严重的不良反应，肿瘤对免疫检查点抑制剂的耐药性仍然是一个尚未解决的挑战。迫切需要新的癌症治疗方法。大量研究表明，IL-35可以招募免疫抑制细胞，通过促进免疫细胞转化为肿瘤生长促进表型以及促进肿瘤血管生成来实现肿瘤免疫逃逸。IL-35 中和抗体被发现可以增强吉西他滨的化疗效果并显着降低微血管密度。因此，靶向 TME 中的 IL-35 提供了一个有前景的癌症治疗靶点。此外，IL-35在不久的将来可能会作为一些肿瘤的独立预后因素。本综述旨在揭示肿瘤微环境中IL-35与免疫细胞的相互作用，这可能为癌症治疗提供新的选择。