肿瘤微环境中免疫检查点糖基化对免疫治疗策略的影响

Impact of immune checkpoint glycosylation in the tumor microenvironment on immunotherapy strategy

糖基化是一种普遍且重要的蛋白质翻译后修饰,相较正常组织,肿瘤组织存在高度异常的蛋白糖基化改变。肿瘤微环境中的免疫检查点常发生糖基化,且其糖基化形式具有稳定蛋白和调控蛋白功能的作用。诸如程序性细胞死亡受体1(programmed death-1, PD-1)、程序性细胞死亡配体1(programmed death ligand 1, PD-L1)等免疫检查点分子均存在多个N-糖基化位点,糖基化修饰防止其被蛋白酶体降解,下调抗肿瘤免疫,诱导肿瘤细胞发生免疫逃逸。本文针对肿瘤免疫微环境中的免疫检查点分子,综述糖基化修饰对该类分子表达及功能的影响,以期通过糖基化干预这一新策略,提高肿瘤免疫检查点阻断治疗的疗效。

Glycosylation is a ubiquitous and crucial post-translational protein modification,and tumor tissues have significantly aberrant protein glycosylation alterations as compared to normal tissues.Immune checkpoints are frequently glycosylated in the tumor microenvironment,and their glycosylated forms play a role in protein stabilization and regulation of protein functions.Immunological checkpoint molecules with numerous N-glycosylation sites,such as programmed death-1(PD-1)and programmed death ligand 1(PD-L1),contain glycosylation alterations that impede proteasome breakdown,reduce anti-tumor immunity,and increase immune escape of tumor cells.This paper reviews the effects of glycosylation modification on the expression and function of immune checkpoint molecules in the tumor immune microenvironment,and we anticipate that a new glycosylation intervention strategy will improve the efficacy of tumor immune checkpoint blockade therapy.