ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1557461
This article is part of the Research TopicPANoptosis and its role in T cell-based immunotherapyView all 7 articles
Interplay between tumor mutation burden and the tumor microenvironment predicts the prognosis of pan-cancer anti-PD-1/PD-L1 therapy
Provisionally accepted
Wuyuan Liao1
Xinwei Zhou1
Hansen Lin1Zihao Feng1Yuhang Chen1Minyu Chen1
Lin Mingjie1Gaosheng Yao1Jinwei Chen1Haoqian Feng1Yinghan Wang1Zhiping Tan1Youyan Tan2
Xinyan Chen3Jun Lu1Pengju Li1Li Luo1
Jinhuan Wei1
Liang-min Fu1,4*- 1The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
- 2Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China
- 3Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
- 4Department of Urology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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Immune checkpoint inhibitor (ICI) therapy plays an essential role in managing advanced cancers. Tumor mutation burden (TMB) has been widely investigated as a biomarker for immunotherapy in recent years. Although the predictive ability of TMB for ICI therapy has been demonstrated in some tumors, its application still has limitations. This study aimed to further investigate the interplay between TMB and the tumor microenvironment (TME) and identify predictive biomarkers for ICI therapy across multiple cancer types. By reviewing and collecting data from The Cancer Genome Atlas (TCGA) pan-cancer and current ICI therapy clinical trials, we validated the predictive capacity of TMB across diverse immune phenotypes and identified genes associated with the TME. Based on these genes, we established a risk signature that showed reliable prognostic predictive ability in ICI cohorts and TCGA pan-cancer. Remarkably, the risk score was linked to stromal components and an immunosuppressive TME. Furthermore, we found that RPLP0 was the most robust predictive marker during model building. Then we demonstrated the abnormal expression of RPLP0 in tumors. With the subcutaneous bladder cancer model, we revealed that intratumor RPLP0 knockdown could improve the immunotherapeutic efficacy. In conclusion, our risk model was a reliable tool, which can be complemented with TMB to provide a precise treatment decision. Through this article, we hope to provide new ideas and targets for ICI therapy across multiple cancer types.
Keywords: Immune checkpoint inhibitor, Tumor mutation burden, Tumor Microenvironment, Pan-cancer, biomarker
Received: 08 Jan 2025; Accepted: 02 Jul 2025.
Copyright: © 2025 Liao, Zhou, Lin, Feng, Chen, Chen, Mingjie, Yao, Chen, Feng, Wang, Tan, Tan, Chen, Lu, Li, Luo, Wei and Fu. 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: Liang-min Fu, Department of Urology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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