ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Circulating PD-1+ effector memory T cells predict anti-PD-1 efficacy in advanced gastric cancer
Provisionally accepted
- 1The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 China., Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, China
- 2Nanjing Medical University, Nanjing, China
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Background: Although standard chemotherapy combined with immunotherapy represented by programmed cell death -1(PD-1) blockade shows promise as a treatment approach for gastric cancer (GC), the drug response rates remain low. Identifying reliable biomarkers to predict patient response is urgently needed. Methods: We collected baseline (before receiving PD-1 inhibitors) peripheral blood samples from advanced GC patients (n=54) who underwent PD-1 inhibitors and platinum drugs from January 2022 to December 2023 and investigated PD-1 expression on effector memory T (TEM) between responders and non-responders according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines by low-dose computed tomography scan evaluation. Univariate and multivariate analyses were applied to identify potential predictive biomarker for chemo-immunotherapy combinations outcomes. In vitro cytotoxicity and cytokine detection were used to demonstrate the effects of PD-1 blockade on TEM cells with different levels of PD-1 expression. Results: The optimal cutoff values for percentages of PD-1+ cells in TEM were 8.66%. Among advanced GC patients receiving anti-PD-1 therapy, responders exhibited a higher mean percentage of PD-1+ cells in TEM (P=0.017) than non-responders, which were associated with longer PFS. Univariate and multivariate Cox regression analyses demonstrated that higher percentage of PD-1+ cells in TEM (HR=0.191, 95% CI 0.065–0.560, P=0.003) was independent protective factor in advanced GC patients receiving chemo-immunotherapy. In vitro, PD-1 blockade enhanced TEM activation, as evidenced by increased cytotoxicity and IFN-γ secretion, leading to improved anti-tumor capacity. Conclusion: Our data identify a high pretreatment percentage of PD-1+ cells in TEM as a potential predictive biomarker for response to PD-1 blockade.
Keywords: effector memory T cells, PD-1, Immunotherapy, biomarker, gastric cancer, peripheralblood
Received: 08 Oct 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Wang, Shao, Xin, Zhang, Liu, Chen and Liu. 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: Wenxiu Chen
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