TRAF3IP3调控T细胞活性与肿瘤免疫的分子机制

项目名称： TRAF3IP3调控T细胞活性与肿瘤免疫的分子机制

项目编号： No.31670896

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 生物科学

项目作者： 邹强

作者单位： 上海交通大学

项目金额： 25万元

中文摘要： 增强T细胞活性的免疫治疗是治疗肿瘤的有效策略，然而抑制T细胞活性的负调控机制限制了免疫治疗的疗效。申请人前期工作鉴定了一些抑制肿瘤免疫中T细胞活性的靶点，并通过应用靶向治疗与免疫治疗协同治疗的策略，有效的提高了肿瘤免疫治疗效果。申请人近期的研究发现TRAF3IP3抑制T细胞的激活，控制调节性T细胞的免疫抑制功能，我们推测TRAF3IP3影响肿瘤免疫与免疫治疗。本项目将在分子和细胞水平上研究TRAF3IP3抑制T细胞激活和控制调节性T细胞功能的分子机制，应用基因敲除小鼠和不同肿瘤模型，解析TRAF3IP3对肿瘤免疫中T细胞活性的调节作用，分析靶向抑制TRAF3IP3对免疫治疗的影响，期望为提高免疫治疗效果和开发肿瘤药物提供新靶点和新策略。

中文关键词： 肿瘤免疫；免疫逃逸；免疫卡控点（immune；checkpoint）；炎症因子

英文摘要： Immunotherapy for enhancing T cell activity is a valuable strategy for tumor therapy. However, the clinical success of immunotherapy has shown to be limited because of the negative mechanisms regulating T cell activity. Our previous studies identify some targets that inhibit T cell antitumor activity and provide strategies to enhance the efficiency of tumor immunotherapy through combining targeted therapies and immunotherapy. Recently, we found that TRAF3IP3 suppressed T cell activation and controlled immunosuppressive function of regulatory T (Treg) cells. We hypothesize that TRAF3IP3 impacts antitumor immunity and immunotherapy. In this application, we propose to investigate the mechanisms of TRAF3IP3 regulating T cell activation and Treg function at the molecular and cellular levels. Furthermore, we will generate knockout mice and use different tumor models to explore the role of TRAF3IP3 on T cell antitumor activity and evaluate the effect of targeting TRAF3IP3 on tumor immunotherapy. Our study holds promise for providing new therapeutic targets and strategies for the improvement of immunotherapy and the development of antitumor drugs.

英文关键词： antitumor immunity;immune evasion;immune checkpoint;inflammatory factors