PD-1/PD-L1的糖基化修饰对肿瘤免疫治疗影响的研究进展

 糖基化修饰是一种重要的蛋白质翻译后修饰，程序性细胞死亡分子1（programmed cell death-1，PD-1）/程序性细胞死亡分子配体1（programmed cell death ligand-1，PD-L1）存在多个N-糖基化位点，其糖基化修饰显著影响免疫治疗的疗效。PD-1共有4个N-糖基化位点，分别为N49、N58、N74和N116。核心岩藻糖基转移酶8（fucosyltransferase 8，FUT8）可催化PD-1的核心岩藻糖基化。一些针对PD-1的N58位点糖基化修饰的单克隆抗体可以有效阻断PD-1/PD-L1相互作用。此外，阻断嵌合抗原受体T细胞（chimeric antigen receptor T-cell，CAR-T）PD-1的N74糖基化修饰可以增强其杀伤效应。PD-L1同样含有4个糖基化位点，分别为N35、N192、N200和N219。一些重要的调控分子可以抑制或促进PD-L1的糖基化修饰，产生一定生物学效应。本文通过综述糖基化修饰对PD-1/PD-L1分子表达及功能的影响，期望为提高肿瘤免疫治疗的疗效提供基于糖基化修饰的新策略。

Research progress on the impact of PD-1/PD-L1 glycosylation on tumor immunotherapy

Glycosylation is an important protein post-translational modification. Both programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are heavily glycosylated and their glycosylation significantly affects the efficacy of immunotherapy.There are four N-glycosylated sites of PD-1, including N49, N58, N74 and N116. Fucosyl transferase 8 (FUT8) can catalyze the core fucosylation of PD-1.Monoclonal antibodies targeting at the N58 site of PD-1 can effectively block the PD-1/PD-L1 interaction. In addition, blocking N74 glycosylation site of PD-1 of chimeric antigen receptor T-cell (CAR-T) can enhance its killing effect.PD-L1 also has four glycosylation sites, namely, N35, N192, N200 and N219.Inhibition or promotion of the glycosylation of PD-L1 can result in certain biological effects.In this review, we summarized the impact of glycosylation on the expression and function of PD-1/PD-L1, aiming to provide novel insights based on glycosylation for improving the efficacy of tumor immunotherapy.