肿瘤免疫治疗近来展现了强大的威力，美国FDA批准的第一个治疗型肿瘤疫苗就是针对前列腺癌，提示免疫治疗可能是攻克前列腺癌的重要突破口。本课题将在自发前列腺癌模型中，探索可行的免疫治疗方法。在证实传统树突细胞疫苗与PD-1抗体联合治疗无效的基础上，我们创新疫苗制备方法，研发了前列腺癌的经典树突细胞（cDC）疫苗，其与PD-1抗体联合后显著抑制前列腺癌的进展。本课题将在多种前列腺癌模型中验证此方法的有效性及在不同类型前列腺癌中的适用情况。同时我们探索优化鼠（人）cDC细胞的诱导方法，解决将来临床应用中细胞来源的问题。机制研究中我们发现，PD-1抗体会增加T细胞共激活分子ICOS的表达，cDC细胞疫苗加入后则可显著增加ICOS+ T细胞的增殖和肿瘤部位浸润。我们将进一步探讨ICOS-ICOSL信号通路在联合治疗中发挥的作用。本课题将促进前列腺癌新型免疫治疗方法的转化，以期使前列腺癌患者尽早受益。

Tumor immunotherapy shows powerful on several types of cancer lately, and the first therapeutic tumor vaccine approved by American FDA is for prostate cancer, suggesting that immunotherapy may be an important breakthrough for conquering prostate cancer. This project will explore feasible immunotherapies in spontaneous prostate cancer mouse models. Based on the fact that combination therapy with traditional DC tumor vaccine and PD-1 Ab had no effect on treatment of prostate cancer, we modified the preparation method of DC vaccine and developed the conventional dendritic cell (cDC) tumor vaccine. The preliminary data showed that cDC tumor vaccine combined with PD-1 Ab dramatically inhibited the progression of prostate cancer. This project will confirm the effect of the combination in multiple prostate mouse model and figure out the range of application. At the same time, we will try to modify the induction method of cDC in vitro to satisfy the needs of cDC cells in future clinical application. For the study on mechanism, we found that treatment of PD-1 Ab can increase the expression of ICOS on T cells, and the addition of cDC tumor vaccine can enhance the proliferation of ICOS+ T cells and their migration into tumor site. We will further explore the role of ICOS-ICOSL pathway on the combination therapy. This project will promote the immunotherapy of prostate cancer to translate into clinic, and benefit prostate cancer patient as early as possible.