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.

中文翻译：

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外泌体 PD-L1 在癌症免疫治疗中的临床意义

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) 信号轴可重振抗肿瘤免疫反应，并具有显着的临床疗效。然而，低反应率限制了免疫疗法对少数患者的益处。最近的研究探索了 PD-L1 作为外泌体中跨膜蛋白的重要性，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 细胞效应器功能，诱导全身免疫抑制，并将功能性 PD-L1 转移到肿瘤微环境 (TME)。由于其对免疫逃逸的重要贡献，外泌体 PD-L1 已被提议作为预测免疫治疗反应和评估治疗效果的生物标志物。在这次审查中，我们总结了外泌体PD-L1的免疫学机制，重点关注导致外泌体生物发生和释放的因素。接下来，我们回顾了外泌体 PD-L1 对 T 细胞功能的影响及其在整个 TME 中的作用。此外，我们讨论了使用外泌体 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 作为肿瘤进展的关键介质，并强调了随后对免疫肿瘤学的临床意义，讨论了靶向外泌体以推进癌症治疗的潜力。我们讨论了使用外泌体 PD-L1 作为癌症免疫治疗的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 作为肿瘤进展的关键介质，并强调了随后对免疫肿瘤学的临床意义，讨论了靶向外泌体以推进癌症治疗的潜力。我们讨论了使用外泌体 PD-L1 作为癌症免疫治疗的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 作为肿瘤进展的关键介质，并强调了随后对免疫肿瘤学的临床意义，讨论了靶向外泌体以推进癌症治疗的潜力。