SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1617905
This article is part of the Research TopicCommunity Series in Biomarkers in the Era of Cancer Immunotherapy: Zooming in from Periphery to Tumor Microenvironment, Volume IIIView all 8 articles
Association between the expression status of programmed cell death ligand 1 and the efficacy of pan-cancer neoadjuvant immune checkpoint blockade
Provisionally accepted
- Quanzhou first hospital, Quanzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background Immune checkpoint inhibitors (ICIs)-based neoadjuvant therapy has been regulatory approved in clinical practice since 2021. However, it is still difficult to determine which patients can benefit from it. Here, we conducted a meta-analysis to evaluate the predictive values of programmed cell death ligand 1 (PD-L1) in pan-cancer neoadjuvant immunotherapy. Methods We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) to collect information regarding pathological complete response (pCR) and event-free survival (EFS) in patients with PD-L1-positive and PD-L1-negative tumors. Odd ratio (OR), hazard ratio (HR), and their 95% confidence intervals (CIs) were calculated. Results Totally, 10353 patients with 6 tumor types in 23 RCTs were included in this study. Neoadjuvant immunotherapy was associated with increased pCRs in both patients with PD-L1-positive (OR, 3.22; 95% CI, 2.25-4.61; P<0.001) and PD-L1-negative tumors (OR, 2.07; 95% CI, 1.42-3.00; P<0.001). However, compared with PD-L1 negative tumors, PD-L1 positive tumors benefited more from ICB-based neoadjuvant therapy (interaction effect, 0.65; 95% CI, 0.45-0.94; PInteraction=0.01). Similarly, neoadjuvant immunotherapy resulted in favorable EFS in patients with PD-L1 positive (HR, 0.55; 95% CI, 0.46-0.66; P<0.001) and PD-L1 negative tumors (HR, 0.70; 95% CI, 0.62-0.80; P<0.001), the efficacy differences were also significant (interaction effect, 1.24; 95% CI, 1.03-1.50; PInteraction=0.04). Conclusion Both patients with PD-L1-positive and PD-L1-negative tumors can benefit from neoadjuvant immunotherapy. However, the magnitude of efficacy is greater in patients with PD-L1-positive tumors. Accordingly, rather than serving as an independent marker for patient selection, PD-L1 expression is more effectively applied as a prognostic biomarker.
Keywords: Cancer, Immunotherapy, PD-L1, Neoadjuvant Therapy, pathologic completeresponse, event-free survival
Received: 25 Apr 2025; Accepted: 17 Sep 2025.
Copyright: © 2025 Huang, Xie, Wang, Lin, Chen, Zhao and Huang. 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: Bin Zhao, doctorbinzhao@126.com
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.