Lab of Chemical Biology and Molecular Drug Design, Institute of Drug Development & Chemical Biology, College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310014, China.
Cells. 2021 Nov 19;10(11):3247. doi: 10.3390/cells10113247.
Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.
程序性细胞死亡配体 1（PD-L1）与其受体程序性细胞死亡蛋白 1（PD-1）的结合可导致细胞毒性 T 淋巴细胞失活，这是肿瘤免疫逃逸的机制之一。基于该机制的免疫疗法已在临床上应用，但仍存在一些问题，如耐药性。肿瘤细胞来源的外泌体 PD-L1 被认为在介导耐药性中起关键作用。本文总结并讨论了各种肿瘤来源的外泌体和肿瘤来源的外泌体 PD-L1 对肿瘤进展的影响。研究人员发现，外泌体 PD-L1 的高表达可在体外实验中抑制 T 细胞的激活，但外泌体 PD-L1 在体内的功能仍存在争议。此外，循环外泌体 PD-L1 具有作为评估临床疗效的指标的高潜力。此外，还讨论了针对外泌体 PD-L1 的治疗策略，如抑制外泌体的生物发生或分泌。此外，还总结了一些基于抑制外泌体策略的具体方法。进一步研究外泌体 PD-L1 可能为肿瘤治疗提供一种有效且安全的方法，而通过抑制外泌体来靶向外泌体 PD-L1 可能是肿瘤治疗的一种潜在方法。
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