REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1603855

Exosomal PD-L1 Detection in Cancer Predictive Biomarker for Response to Immune Checkpoint Blockade Therapy

Provisionally accepted
Tetsuichi KanshaTetsuichi Kansha1,2,3Xiaojuan MaXiaojuan Ma1,2,3Hao WangHao Wang1,2,3Xiaotong YuXiaotong Yu1,2,3Ying SongYing Song1,2,3Zhengyang GuoZhengyang Guo1,2,3Jiagui SongJiagui Song1,2,3Lixiang XueLixiang Xue1,2,3*Jianling YangJianling Yang1,2,3*
  • 1Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China
  • 2Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Beijing, China
  • 3Cancer Center of Peking University Third Hospital, Beijing, China

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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 membranebound 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.

Keywords: exosomal PD-L1, Cancer biomarkers, Early detection, liquid biopsy, Immune checkpoint blockade

Received: 01 Apr 2025; Accepted: 02 Jun 2025.

Copyright: © 2025 Kansha, Ma, Wang, Yu, Song, Guo, Song, Xue and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Lixiang Xue, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China
Jianling Yang, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material