Wang Jing, Zeng Hao, Zhang Hongwei, Han Yunwei
Department of blood transfusion, the affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Southwest Medical University, Luzhou, Sichuan, China.
Transl Oncol. 2021 May;14(5):101047. doi: 10.1016/j.tranon.2021.101047. Epub 2021 Feb 26.
Exosomes are bioactive lipid bilayer vesicles released by most cells to mediate intercellular signal communication. Tumor cells release exosomes transmitting signals cell-to-cell and between cells and organs, which will promote tumor angiogenesis, regulate tumor stromal response, immune response, and enhance tumor cells resistance, while exosomes-derived from immune cells in tumor microenvironment play a key role in inhibiting tumor growth and killing tumor cells. Programmed cell death protein 1 (PD-1) combined with Programmed cell death protein ligand 1(PD-L1) can inhibit the activation of T cells, for tumor cells achieve immune escape by overexpressing PD-L1 and binding PD-1 on T cells. The use of anti-PD-1 / PD-L1 antibodies prevents their binding to a certain extent and partially restores T cell's activity. This article mainly discusses the role of exosomal PD-L1 in tumor progression and therapeutic efficacy after application of clinical antibodies, as well as the relation between different reactivity and immunity set points in cancer patients of different races, with different types and at different stages. Besides, we propose that exosomal PD-L1 may become targets for anti-PD-1 / PD-L1 antibody therapy, biomarkers for liquid biopsy, and drug carriers.
外泌体是大多数细胞释放的具有生物活性的脂质双层囊泡，用于介导细胞间信号通讯。肿瘤细胞释放的外泌体在细胞间以及细胞与器官之间传递信号，这会促进肿瘤血管生成、调节肿瘤基质反应、免疫反应，并增强肿瘤细胞的抗性，而肿瘤微环境中免疫细胞衍生的外泌体在抑制肿瘤生长和杀伤肿瘤细胞方面起关键作用。程序性细胞死亡蛋白1（PD-1）与程序性细胞死亡蛋白配体1（PD-L1）结合可抑制T细胞的激活，肿瘤细胞通过过度表达PD-L1并与T细胞上的PD-1结合来实现免疫逃逸。使用抗PD-1/PD-L1抗体在一定程度上阻止它们的结合，并部分恢复T细胞的活性。本文主要探讨外泌体PD-L1在肿瘤进展中的作用以及临床应用抗体后的治疗效果，以及不同种族、不同类型和不同阶段癌症患者中不同反应性与免疫设定点之间的关系。此外，我们提出外泌体PD-L1可能成为抗PD-1/PD-L1抗体治疗的靶点、液体活检的生物标志物和药物载体。
