Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy.
Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy.
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DOI：
10.1155/2021/8839978
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发表时间：
2021
影响因子：
4.1
通讯作者：
González-Valdez J
中科院分区：
文献类型：
--
作者：
Ayala-Mar S;Donoso-Quezada J;González-Valdez J
抑制程序性细胞死亡配体-1 (PD-L1)/程序性细胞死亡受体-1 （PD-1）信号轴可激活抗肿瘤免疫应答，具有显著的临床疗效。然而，低应答率限制了免疫治疗对少数患者的益处。最近的研究探索了PD-L1作为外泌体跨膜蛋白的重要性，并揭示了外泌体PD-L1作为肿瘤免疫逃逸和免疫治疗抵抗的机制。外泌体PD-L1抑制T细胞效应功能，诱导全身免疫抑制，并在肿瘤微环境（TME）中转移功能性PD-L1。由于其对免疫逃逸的重要贡献，外泌体PD-L1已被提出作为预测免疫治疗反应和评估治疗效果的生物标志物。本文综述了外泌体PD-L1的免疫学机制，重点介绍了导致外泌体生物发生和释放的因素。接下来，我们回顾外泌体PD-L1对T细胞功能的影响及其在TME中的作用。此外，我们还讨论了使用外泌体PD-L1作为癌症免疫治疗生物标志物的最新发现。在这篇综述中，我们提出外泌体PD-L1是肿瘤进展的关键介质，并强调了免疫肿瘤学的临床意义，讨论了靶向外泌体推进癌症治疗的潜力。
Inhibiting the programmed cell death ligand-1 (PD-L1)/programmed cell death receptor-1 (PD-1) signaling axis reinvigorates the antitumor immune response with remarkable clinical efficacy. Yet, low response rates limit the benefits of immunotherapy to a minority of patients. Recent studies have explored the importance of PD-L1 as a transmembrane protein in exosomes and have revealed exosomal PD-L1 as a mechanism of tumor immune escape and immunotherapy resistance. Exosomal PD-L1 suppresses T cell effector function, induces systemic immunosuppression, and transfers functional PD-L1 across the tumor microenvironment (TME). Because of its significant contribution to immune escape, exosomal PD-L1 has been proposed as a biomarker to predict immunotherapy response and to assess therapeutic efficacy. In this review, we summarize the immunological mechanisms of exosomal PD-L1, focusing on the factors that lead to exosome biogenesis and release. Next, we review the effect of exosomal PD-L1 on T cell function and its role across the TME. In addition, we discuss the latest findings on the use of exosomal PD-L1 as a biomarker for cancer immunotherapy. Throughout this review, we propose exosomal PD-L1 as a critical mediator of tumor progression and highlight the clinical implications that follow for immuno-oncology, discussing the potential to target exosomes to advance cancer treatment.
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