泛素连接酶ZFP91在CD8+T细胞抗肿瘤功能中的调控机制

CD8+T细胞是执行抗原专一性杀伤肿瘤细胞的主要效应细胞，认识CD8+T细胞活性的调控机制对增强肿瘤免疫应答和提高肿瘤治疗效果至关重要。申请人已有的研究成果揭示了一些蛋白质翻译后修饰酶在T细胞活性与肿瘤免疫中的调控机制，并通过干预这些酶的功能有效增强了T细胞抗肿瘤活性和肿瘤治疗效果。本项目初步结果显示：泛素连接酶ZFP91抑制CD8+T细胞激活，T细胞条件性敲除ZFP91小鼠具有更强的抗肿瘤免疫反应。鉴于此，推测ZFP91在CD8+T细胞抗肿瘤功能中具有重要作用。本项目将展开以下研究：1.解析ZFP91对CD8+T细胞抗肿瘤免疫反应的调节作用；2.分析ZFP91介导的CD8+T细胞信号通路；3.鉴定CD8+T细胞中ZFP91的作用靶点及其功能。项目研究成果将为理解CD8+T细胞活性的调控机制提供新的理论依据，为肿瘤药物开发提供新的靶标，为增强肿瘤治疗效果提供新的策略。

CD8+ T cells can kill tumor cells in an Ag-specific manner and play a central role in cell-mediated tumor clearance. Understanding the molecular mechanisms regulating CD8+ T cell activity is essential for the enhancement of antitumor immune responses and tumor therapy. In our previous study, we had demonstrated that some important post-translational modification enzymes inhibited antitumor T cell responses and targeting these enzymes remarkably improved antitumor T cell activity and tumor therapy. Recently, we found that E3 ubiquitin-protein ligase ZFP91 suppressed CD8+ T cell activation and T cell-specific deletion of ZFP91 enhanced antitumor immune responses in mice. We hypothesize that ZFP91 plays an important role in CD8+ T cell antitumor function. In this application, we propose to investigate the function of ZFP91 in CD8+ T cell antitumor immune responses. Moreover, we will assess ZFP91-mediated signaling pathway in CD8+ T cells. Furthermore, we will identify the target of ZFP91 and define its function in CD8+ T cells. Our study not only highlights the role of ZFP91 in the molecular mechanisms regulating CD8+ T cell activity, but also holds promise for providing new therapeutic targets and strategies for the development of antitumor drugs and the improvement of tumor therapy.