论文部分内容阅读
肿瘤组织中T细胞表面的程序性细胞死亡1受体（PD-1）和肿瘤细胞分泌的程序性死亡配体1（PD-L1）的过度表达在一定程度上抑制了机体的细胞免疫反应，从而使肿瘤细胞的生长得以逃避免疫系统的监视和清除。PD-1/PD-L1抑制剂就是针对PD-1或PD-L1表达设计的特定蛋白质抗体，可阻止PD-1和肿瘤细胞上PD-L1相互作用，进而部分恢复T细胞功能，增强T细胞杀死肿瘤细胞的作用。然而，在临床应用中，PD-1/PD-L1抑制剂的耐药问题越来越凸显，部分患者的疗效不能持久，甚至无应答。近年来的研究发现，PD-1与PD-L1表达受许多免疫因子调控，PD-L1的转运和降解等过程也会受到糖基化、磷酸化、泛素化等多种因素的影响。对一些可能干预PD-1/PD-L1通路的调控因子的研究将有助于发现新的治疗策略，克服肿瘤对PD-1/PD-L1抑制剂耐药，改善肿瘤免疫治疗效果。“,”The overexpression of programmed cell death 1 receptor (PD-1) on the surface of T cells and programmed cell death 1 ligand 1 (PD-L1) secreted by tumor cells in tumor tissue inhibits the cellular immune response to a certain degree, so that the growth of tumor cells can escape the surveillance and clearance of the immune system. PD-1/PD-L1 inhibitors are specific protein antibodies designed for the expression of PD-1 or PD-L1, which can prevent the interaction between PD-1 and PD-L1 on tumor cells, thus partially restore T cell function and enhance tumor cell killing by T cells. However, because of the increasingly prominent drug resistance of PD-1/PD-L1 inhibitors in clinical applications, their efficacy cannot be sustained or even there were non-response to drugs in some patients. Recent studies have found that the expression of PD-1 and PD-L1 is regulated by many immune factors, and the transport and degradation processes of PD-L1 are also affected by many factors, such as glycosylation, phosphorylation, ubiquitination, and so on. The researches on the regulatory factors that may interfere in the PD-1/PD-L1 pathway will help to develop new treatment strategies to overcome drug resistance of PD-1/PD-L1 inhibitors in tumor, thereby improving the efficacy of tumor immunotherapy.