PD-L1降解途径与肿瘤免疫治疗

PD-L1 Degradation Pathway and Cancer Immunotherapy

摘要

程序性死亡受体配体1 (programmed death ligand 1, PD-L1)是肿瘤免疫检查点阻断治疗中的重要靶点, 其在多种细胞中均有表达。肿瘤细胞可通过高表达PD-L1来增强程序性死亡受体1 (programmed death 1, PD-1)抑制信号, 从而促进肿瘤免疫逃逸。近年来, 以抗PD-1/PD-L1抗体为代表的肿瘤免疫治疗给癌症治疗带来了革命性的变化。然而, 肿瘤免疫治疗仅能对部分患者产生持久的疗效, 多数患者对肿瘤免疫治疗的应答短暂或没有应答。研究发现, PD-L1的降解对肿瘤免疫治疗应答至关重要。本文综述了PD-L1的溶酶体降解途径、蛋白酶体降解途径及PD-L1降解与肿瘤免疫治疗的相互作用, 旨在为进一步增强肿瘤免疫治疗的应答率和应答范围提供研究思路。

Abstract

Programmed death ligand 1 (PD-L1) has emerged as an important target in immune checkpoint blo-ckade therapy for cancer. It is expressed in a variety of cells. Its high expression in tumor cells can enhance programmed death 1 (PD-1) inhibitory signals, thus promoting tumor immune escape. In recent years, cancer immunotherapy based on anti-PD-1/PD-L1 antibodies has brought revolutionary changes in cancer treatment. However, cancer immunotherapy produces long-lasting treatment effects only in some people with cancer. For most patients, it has short-term or no effects. Studies have found that the degradation of PD-L1 is critical for treatment response to cancer immunotherapy. Herein, the lysosomal and proteasomal pathways of PD-L1 degradation and the interaction of PD-L1 degradation with cancer immunotherapy are reviewed, aiming to provide new ideas for improving response rate and scope in cancer immunotherapy.

关键词

程序性死亡受体配体1 (PD-L1) / 溶酶体降解途径 / 蛋白酶体降解途径 / 肿瘤免疫治疗

Key words

programmed death ligand 1 (PD-L1) / lysosomal degradation pathway / proteasomal degradation pathway / cancer immunotherapy