CD8+ T细胞是机体抗肿瘤免疫的主要效应细胞，改善CD8+ T细胞的功能是目前肿瘤免疫治疗的重要手段。研究证明胆固醇代谢可调节CD8+ T细胞的抗肿瘤免疫应答。低密度脂蛋白受体（low density lipoprotein receptor，LDLR）是细胞摄取外源胆固醇的开关分子，其是否参与了CD8+ T细胞的抗肿瘤功能的调控目前尚未见报道。我们前期发现CD8+ T细胞激活后LDLR的表达升高，敲除LDLR的CD8+ T细胞抗肿瘤功能受到抑制。由此可见，LDLR在CD8+T细胞抗肿瘤功能的调控中扮演重要角色。本项目拟通过体内和体外实验，采用淋巴细胞分离、流式细胞术、小鼠移植瘤模型和T细胞过继治疗等实验技术，对LDLR在CD8+ T细胞的抗肿瘤免疫应答中的作用及机制进行系统研究。该项目的实施不仅有助于加深我们对胆固醇代谢调控T细胞抗肿瘤免疫的理论认识，也有望为肿瘤免疫治疗提供新的思路。

CD8+ T cells are central players in antitumor immunity, while their activity is repressed in the tumor microenvironment. Improving the cytotoxicity function of CD8+ T cells is of great clinical interest in cancer immunotherapy. Accumulated studies have demonstrated that cholesterol metabolism can modulate the antitumor activity of CD8+ T cells. Low density lipoprotein receptor (LDLR) is a switch molecule for cellular uptake of exogenous cholesterol. However, whether LDLR is involved in the regulation of antitumor function of CD8+ T cells remains unknown. Our recent study found that the expression of LDLR increased upon CD8+ T cell activation, and deletion of LDLR inhibited the antitumor activity of CD8+ T cells. In this project, we will investigate the role of LDLR in the regulation of antitumor function of CD8+ T cell both in vivo and in vitro by using lymphocyte separation, flow cytometry, mouse xenograft models and T cell adoptive therapy. Our results will shed new light on our understanding of cholesterol metabolism modulation in T cell antitumor immunity. Moreover, our study will provide a potential target for cancer immunotherapy.