Kansha Tetsuichi, Ma Xiaojuan, Wang Hao, Yu Xiaotong, Song Ying, Guo Zhengyang, Song Jiagui, Xue Lixiang, Yang Jianling
Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.
Cancer Center of Peking University Third Hospital, Peking University Third Hospital, Beijing, China.
Front Immunol. 2025 Jul 3;16:1603855. doi: 10.3389/fimmu.2025.1603855. eCollection 2025.
Programmed death-ligand 1 (PD-L1) carried by tumor-derived exosomes has emerged as a critical mediator of immune evasion and resistance to immune checkpoint blockade therapy. Unlike membrane-bound PD-L1, exosomal PD-L1 is systemically distributed and capable of suppressing T cell activity at distant sites. This review summarizes the current understanding of exosomal PD-L1 biogenesis, its immunosuppressive mechanisms, and its clinical relevance across multiple cancer types. We highlight its potential as a non-invasive biomarker for predicting therapeutic response and monitoring disease progression. Compared with tissue-based PD-L1 assessment, exosomal PD-L1 offers advantages in accessibility and dynamic reflection of tumor immune status. However, challenges remain regarding standardization of detection methods and clinical interpretation. Future directions include the integration of exosomal PD-L1 profiling into immunotherapy decision-making and the development of therapeutic strategies targeting exosome secretion. These insights may contribute to overcoming resistance in immunologically inert tumors and advancing precision oncology.
肿瘤来源的外泌体携带的程序性死亡配体1（PD-L1）已成为免疫逃逸和免疫检查点阻断治疗耐药的关键介质。与膜结合的PD-L1不同，外泌体PD-L1在全身分布，能够在远处部位抑制T细胞活性。本综述总结了目前对外泌体PD-L1生物发生、免疫抑制机制及其在多种癌症类型中的临床相关性的理解。我们强调其作为预测治疗反应和监测疾病进展的非侵入性生物标志物的潜力。与基于组织的PD-L1评估相比，外泌体PD-L1在可及性和肿瘤免疫状态的动态反映方面具有优势。然而，检测方法的标准化和临床解释方面仍存在挑战。未来的方向包括将外泌体PD-L1分析纳入免疫治疗决策以及开发针对外泌体分泌的治疗策略。这些见解可能有助于克服免疫惰性肿瘤的耐药性并推动精准肿瘤学的发展。
