摘要
程序性细胞死亡蛋白1(PD-1)及其配体PD-L1是重要的免疫检查点蛋白,肿瘤细胞膜上的PD-L1与T细胞上的PD-1结合以逃避免疫监视。靶向PD-L1/PD-1的免疫疗法在多种肿瘤的治疗中显示出了显著的临床效果,遗憾的是只有一部分患者实现了持久反应。最新研究表明,PD-L1可定位于肿瘤细胞内,发挥着非免疫检查点功能,广泛参与肿瘤细胞的多种恶性表型。全文总结了肿瘤细胞内PD-L1作用的相关研究进展,从PD-L1胞内定位的调控,以及胞内PD-L1与DNA损伤修复、细胞自噬、细胞凋亡、肿瘤转移的关系,论述了胞内PD-L1与肿瘤细胞恶性表型的关系。最后,介绍了靶向胞内PD-L1的策略方法,为靶向PD-L1的癌症治疗提供思路。
Programmed cell death protein 1(PD-1)and its ligand PD-L1 are important immune checkpoint proteins.In tumor cells,PD-L1 is mainly located on cell membranes,which binds to PD-1 on T cells to evade immune surveillance.Immunotherapies targeting PD-L1/PD-1 have shown significant results in the treatment of various tumors,but unfortunately,only a subset of patients have achieved a consistent response.Latest studies have shown that PD-L1 can be also localized in tumor cells(intracellular PD-L1),playing a non-immune checkpoint function,and involving in various malignant phenotypes of tumor cells.This paper reviews the research progress on the role of intracellular PD-L1(intra-PD-L1)in tumor cells;discusses the relationship between intra-PD-L1 and the malignant phenotype of tumor cells,focusing on the regulation of intracellular localization of PD-L1,the relationship of intra-PD-L1 with DNA damage repair,autophagy,apoptosis and tumor metastasis,as well as the strategy of targeting intra-PD-L1 for clinical cancer treatment.
作者
徐轲
吴华鑫
林超男
张晓冉
罗文龙
龚立豪
李金龙
XU Ke;WU Huaxin;LIN Chaonan;ZHANG Xiaoran;LUO Wenlong;GONG Lihao;LI Jinlong(School of Laboratory Medicine and Biotechnology,Southern Medical University,Guangzhou 510515,China;School of Basic Medicine,Southern Medical University,Guangzhou 510515,China)
出处
《中国肿瘤》
CAS
CSCD
北大核心
2023年第9期714-722,共9页
China Cancer
基金
国家自然科学基金(81672915)
广东省自然科学基金(2022A1515010515)。
