PD-1/PD-L1通路及其抗体耐药机制的研究进展

Research progress of PD-1/PD-L1 pathway and resistance mechanism of its antibodies

程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)能通过调节细胞信号通路和表观遗传修饰来抑制T细胞、B细胞的增殖和效应作用。近几年来,在多种恶性肿瘤中,PD-1/PD-L1通路的免疫检查点抑制剂取得了令人惊喜的临床治疗效果,但随之而来的原发性和继发性耐药成为了新的问题,不仅影响了PD-1/PD-L1抗体的治疗效果,也限制了其在临床的广泛应用。本文就PD-1/PD-L1相关信号通路以及导致PD-1/PD-L1抗体耐药的相关机制作一综述。

Programmed death 1(PD-1)and its ligand(PD-L1)can inhibit the proliferation and function of T and B cells by regulating cellular signaling pathways and epigenetic modifications.In the past decade,immune checkpoint blockades,such as inhibitors against PD-1/PD-L1,have received surprising clinical response in a variety of malignant tumors.However,the subsequent primary and acquired resistance has become a new problem,which not only influences long-lasting response of PD-1/PD-L1 blockade therapy,but also limits its wide application in clinic.This paper will make a review on the related mechanisms of the regulation of PD-1/PD-L1 pathway and the resistance to PD-1/PD-L1 blockade therapy.