靶向免疫检查点PD-1的治疗在多种恶性肿瘤中显示了惊人的疗效，但仍有部分患者对靶向PD-1的免疫治疗无反应。我们前期研究结果显示：PD-1在低反应性MAGE-A3特异性CD8+T细胞表面高表达；而应用PD-1/PD-L1阻断剂后仅能轻度增强CD8+T细胞的增殖能力和功能，因而寻求新的策略以增强靶向PD-1免疫治疗的疗效是肿瘤免疫治疗领域的研究热点。数据库分析发现PD-1正向调控脂类代谢，而脂类代谢同活性氧密切相关；活性氧的失衡将影响T细胞的活化和功能，预实验结果显示活性氧清除剂谷胱甘肽能够减少 PD-1+ CD8+T细胞的凋亡并增强其分泌IFN-r的能力；因而我们提出假说，PD-1+CD8+T细胞表达更高水平的活性氧，PD-1/PD-L1阻断剂对活性氧的水平无影响；我们将进一步探讨谷胱甘肽联合PD-1/PD-L1阻断剂增强 CD8+T细胞抗肿瘤作用的机制。

Targeting immune checkpoints PD-1 in the treatment of various malignant tumors have been obtaining curative effects，however， some patients still have no response due to the resistance to PD-1 therapy. In preliminary study, the level of PD-1 expression was higher on the surface of nonresponsive MAGE-A3 specific T cells, but the proliferation and function of PD-1 positive CD8+ T cells were partially reinvigorated by PD-1/PD-L1 blockade. Thus, it is a hot area to explore novel strategy to enhance the effect of targeting PD-1 immunotherapy. Database results showed that PD-1 was positively associated the lipid metabolism that was closed to reactive oxygen species. It was reported that the unbalance of ROS could influence the activation and function of T cells. Preliminary test results showed that ROS scavenger glutathione (GSH) could reduce the apoptosis and improve the function of PD-1+ CD8+T cells. Therefore, we propose the hypothesis that ROS level is higher and could not be affected by PD-1/PD-L1 blockade in PD-1+CD8+T cells , we further explore the mechanism that how combing GSH with PD-1/PD-L1 blockade improve the antitumor ability of CD8+T cells.