Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies.
Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies.
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外泌体 PD-L1：肿瘤免疫逃逸机制和治疗策略的新见解
DOI：
10.3389/fcell.2020.569219
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发表时间：
2020
影响因子：
5.5
通讯作者：
Liang G
中科院分区：
文献类型：
--
作者：
Zhou K;Guo S;Li F;Sun Q;Liang G
作为一种经典的免疫检查点分子，肿瘤细胞表面的PD-L1在肿瘤免疫抑制中起着关键作用，主要通过与其受体PD-1结合来抑制T细胞的抗肿瘤活性。PD-1/PD-L1抑制剂在治疗各种人类癌症方面表现出前所未有的前景，具有令人印象深刻的疗效。然而，很大一部分癌症患者的反应仍然较低。因此，更好地了解PD-L1介导的免疫逃逸是必要的。PD-L1可以在肿瘤细胞表面表达，但也发现它以细胞外形式存在，例如在外来体上。最近的研究揭示了外泌体PD-L1（ExoPD-L1）的重要性。作为膜结合PD-L1的替代物，肿瘤细胞产生的ExoPD-L1在抗肿瘤免疫应答中也发挥着重要的调节作用。本文综述了ExoPD-L1生物学功能的最新研究成果，包括抑制淋巴细胞活性、向PD-L1阴性肿瘤细胞和免疫细胞迁移、诱导局部和全身免疫抑制以及促进肿瘤生长。我们还讨论了ExoPD-L1作为疾病进展和治疗反应的预测因子的潜在意义，检测循环ExoPD-L1的敏感方法，以及在临床中将外泌体生物合成抑制与PD-L1阻断相结合的新型治疗策略。
As a classical immune checkpoint molecule, PD-L1 on the surface of tumor cells plays a pivotal role in tumor immunosuppression, primarily by inhibiting the antitumor activities of T cells by binding to its receptor PD-1. PD-1/PD-L1 inhibitors have demonstrated unprecedented promise in treating various human cancers with impressive efficacy. However, a significant portion of cancer patients remains less responsive. Therefore, a better understanding of PD-L1-mediated immune escape is imperative. PD-L1 can be expressed on the surface of tumor cells, but it is also found to exist in extracellular forms, such as on exosomes. Recent studies have revealed the importance of exosomal PD-L1 (ExoPD-L1). As an alternative to membrane-bound PD-L1, ExoPD-L1 produced by tumor cells also plays an important regulatory role in the antitumor immune response. We review the recent remarkable findings on the biological functions of ExoPD-L1, including the inhibition of lymphocyte activities, migration to PD-L1-negative tumor cells and immune cells, induction of both local and systemic immunosuppression, and promotion of tumor growth. We also discuss the potential implications of ExoPD-L1 as a predictor for disease progression and treatment response, sensitive methods for detection of circulating ExoPD-L1, and the novel therapeutic strategies combining the inhibition of exosome biogenesis with PD-L1 blockade in the clinic.