新型调节细胞因子IL-35可通过影响调节性T细胞(regulatory T cell, Treg)功能介导肿瘤免疫逃逸。我们前期研究发现Treg在前列腺癌(prostate cancer, PCa) 冷冻免疫中亦扮有重要角色，采用CTLA-4单抗阻断Treg功能明显提高冷冻治疗效果。同时还发现，IL-35在PCa患者血浆中的水平高于健康对照，且PCa组织、肿瘤细胞及培养上清中均可见IL-35表达。由此推测，IL-35可能通过多种机制参与PCa发生发展，并通过介导免疫逃逸影响冷冻免疫反应。鉴于此，本项目将以IL-35为切入点，(1)分析IL-35在PCa中的表达及其临床意义；(2) 探讨IL-35在PCa发生发展和肿瘤免疫中的作用及机制；(3) 分析IL-35在PCa冷冻免疫中的作用，探讨IL-35单抗联合冷冻消融治疗PCa的有效性及其机制，以期为PCa综合治疗提供新思路。

Novel regulatory cytokine IL-35 may contribute to tumor immune escape via Treg. Our previous study found that Treg played an important role in cryo-immunological response of prostate cancer (PCa); efficacy of cryoablation were enhanced significantly by CTLA-4 monoclonal antibody blockade. Meanwhile, we also found that serum IL-35 levels of PCa patients was significantly higher than healthy controls, IL-35 were also detected in PCa tissue, tumor cell lines, and culture supernatants. According to these results above, we speculate that IL-35 may invole in Pca progression and cryo-immunological response through many mechanisms (immune response, etc.). Therefore, this project will put IL-35 as a crucial point: (1) analyze the expression and clinical significance of IL-35 in PCa; (2) explore the role and mechanisms of IL-35 in the PCa progression and tumor immunity; (3) analyze the role of IL-35 in cryo-immunological response, and explore the efficacy and mechanisms of IL-35 blockage combined with cryoablation in Pca. All the reseach will provide new ideas for the comprehensive treatment of PCa.