免疫检查点PD-L1上调和前列腺癌（PCa）恩杂鲁胺（ENZ）治疗耐受后的免疫逃避相关。申请者前期研究发现：FLII是雄激素受体（AR）共抑制因子，恢复FLII表达能增强ENZ对PCa治疗的敏感性；FLII和PD-L1负相关并抑制PD-L1表达。据此提出FLII/PD-L1通路是抗雄药物ENZ耐受引起免疫逃避的关键信号通路假说。本项目拟检测PCa临床标本中FLII和PD-L1表达，以ENZ耐受的PCa细胞及和T细胞共培养体系、同源性Tramp小鼠移植瘤模型为研究对象，运用ELISA、流式细胞术等观察FLII/PD-L1调节ENZ耐受引起T细胞的免疫反应，并通过荧光素酶报告基因、染色质免疫共沉淀（ChIP）、基因芯片等手段，检测FLII调节PD-L1机制，以及抗雄治疗耐受引起免疫反应的相关基因表达，以证明该假说，为PCa免疫治疗联合抗雄药物治疗及新型特异分子靶向基因治疗研发提供新策略和思路。

High PD-L1 expression was associated with Enzalutamide resistance-mediated immune evasion. Our previous studies found: FLII functioned as an AR co-repressor and inhibited prostate cancer progression; Re-introduction of FLII in castration-resistant cells sensitized the cells to Enzalutamide treatment. PD-L1 was regulated by FLII. In view of this, we made a scientific hypothesis that FLII / PD-L1 pathway may be an important mechanism for anti-androgen therapy-mediated immune resistance. In this project, we aim to explore the mechanism and function of FLII / PD-L1 on Enzalutamide resistance-mediated immune evasion by ELISA, Flow Cytometry (FCM), Luciferase reporter gene, ChIP and MicroArray in tumor cell/T cell co-culture model and syngeneic orthotopic prostate cancer model.