ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1656242
This article is part of the Research TopicCommunity Series in The Immunosuppressive Tumor Microenvironment and Strategies to Revert its Immune Regulatory Milieu for Cancer Immunotherapy: Volume IIView all 9 articles
PD-1 and LAG-3 were optimal combination of immune checkpoints for predicting poor clinical outcomes of patients with ovarian cancer
Provisionally accepted
- 1Shanghai Jiao Tong University, Shanghai, China
- 2Guangzhou First People's Hospital, Guangzhou, China
- 3Guangzhou Medical University, Guangzhou, China
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Background: Although immune checkpoint blockade (ICB) therapy has transformed the therapeutic landscape for ovarian cancer (OC), the predictive utility of immune checkpoint (IC) expression signatures in stratifying clinical outcomes requires further systematic interrogation.Methods: Transcriptomic profiles from 147 OC patients within The Cancer Genome Atlas (TCGA) cohort were interrogated to assess the prognostic significance of ICs. These genomic findings were subsequently validated through immunohistochemical analysis of an independent institutional cohort comprising 74 OC tissue specimens.Results: Both TCGA and validation cohorts demonstrated that elevated expression of PD-1 and LAG-3 correlated with inferior overall survival (OS) in patients with OC. Importantly, among the ICs, PD-1/LAG-3 co-expression emerged as the optimal combinatorial biomarker, independently predicting adverse outcomes [hazard ratio (HR) = 1.74, 95% confidence interval (CI):1.12-2.70, P < 0.001]. The derived nomogram model incorporating PD-1/LAG-3 status, TNM stage, histologic grade, and age generated patient-tailored 1-5 year OS rate estimates. Notably, risk stratification using this model significantly enhanced prognostic precision versus conventional parameters (TNM stage or histologic grade) alone, especially in patients with serous cystadenocarcinoma.Elevated IC expression correlated with poor OS in OC patients. Specifically, PD-1/LAG-3 co-expression emerged as the optimal prognostic biomarker pair, representing a promising therapeutic target for dual checkpoint blockade strategies in OC.
Keywords: Immune checkpoint, PD-1, LAG-3, prognosis, ovarian cancer
Received: 29 Jun 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Wu, Chen, Cui, Zhou, Yang, Sun, Du and Wang. 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: Peipei Wang, Guangzhou First People's Hospital, Guangzhou, China
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