外泌体程序性死亡配体-1介导肿瘤免疫逃避机制研究进展

Progress on the mechanism of tumor immune evasion induced by exosomal PD-L1

目的外泌体是一种由多种细胞分泌的内含复杂生物活性物质的细胞外囊泡,肿瘤细胞释放的外泌体可表达程序性死亡-配体1(programmed cell death-Ligand 1,PD-L1),并且在肿瘤免疫逃避机制中扮演重要角色。本研究探讨外泌体、程序性死亡受体-1(programmed death 1,PD-1)/PD-L1途径、外泌体PD-L1在肿瘤进展中的重要作用、机制以及相关肿瘤治疗方法,为肿瘤治疗策略提出新思路。方法应用PubMed及中国知网数据库检索系统,以"外泌体、PD-1/PD-L1、肿瘤、免疫逃避、Exosomes、PD-L1、PD-1/PD-L1、Tumor、Immune evasion"等为关键词,检索2000-01-2019-09的相关文献。纳入标准:(1)外泌体、PD-L1与肿瘤相关性的科学研究;(2)外泌体PD-L1介导肿瘤免疫逃避机制相关的研究。排除标准:实验结果重复及数据陈旧的实验研究。根据纳入和排除标准分析中文文献2篇,英文文献39篇。结果外泌体是细胞间信息交流的媒介,内含有多种内容物。最近的研究发现,外泌体携带一种典型的免疫表面蛋白PD-L1,通过与PD-1结合,抑制T细胞的抗肿瘤功能,有效地保护肿瘤不受免疫监视。肿瘤细胞为了抑制免疫系统而释放含有PD-L1的外泌体,对免疫细胞的活性具有远程干扰作用,并且外泌体PD-L1对抗PD-L1抗体阻断具有抵抗力。结论外泌体PD-L1的发现为肿瘤免疫逃避机制提供了新的见解,对当前抗PD-1/PD-L1免疫治疗具有重要的指导意义,可能是朝着精确、个性化的肿瘤医学治疗迈出的一大步。

OBJECTIVE Exosomes are extracellular vesicles containing complex bioactive substances secreted by a variety of cells,the exosome released by tumor cells can carry programmed cell death-Ligand 1(PD-L1)and play an important role in the mechanism of immune escape from tumor.this review describes the important roles of exosomes,programmed death 1(PD-1)/PD-L1 pathway and exosome PD-L1 in the progression of tumor,summarizes its mechanism of action and related tumor treatment methods,and puts forward new ideas for tumor treatment strategies.METHODS PubMed and CNKI retrieval system were used to search for related literatures from 2000-1 to 2019-9,using"exosome,PD-1/PD-L1,tumor,immune evasion"as the key words.Inclusion criteria:(1)Exosomes,PD-L1 and cancer-related scientific research;(2)Studies on the mechanism of immune evasion mediated by exosome PD-L1.Exclusion criteria:Repeated and outdated experimental results.According to the inclusion criteria and exclusion criteria,2 Chinese articles and 39 English articles were analysed.RESULTS Exosomes,as the medium of intercellular information exchange,contain a variety of substances.Exosomes can carry a typical immune surface protein PD-L1,which binds to programmed death receptor-1(PD-1),inhibits the anti-tumor function of T cells and effectively protects tumors from immune surveillance.In order to inhibit the immune system,tumor cells release exosomes containing PD-L1,which can interfere with the activity of immune cells remotely,and exosomal PD-L1 may be resistant to traditional anti-PD-L1 antibodies.CONCLUSIONS The discovery of exosome PD-L1 provides new insights into the mechanism of tumor immune evasion,and has important guiding significance for current anti-PD-1/PD-L1 immunotherapy.It may be a major step towards precise and individualized tumor medical treatment.