ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1596434
This article is part of the Research TopicPrecision Medicine and Targeted Therapies in Gastrointestinal and Genitourinary Solid TumorsView all 11 articles
Pygo2+ T cells possess immunosuppressive features and inferior immunotherapeutic response in gastric cancer
Provisionally accepted
Chang Weilong1
Huifang Yan2Yawei Zhang1Zibo sang3Bei Bu1Rui Deng1Kaibo Li3Jiajing Li1*
Yang Fu1*
Jinyuan Cui1*- 1First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- 2Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- 3Department of Clinical Medicine, The First Clinical Medical College of Zhengzhou University, zhengzhou, China
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Background: Gastric cancer (GC) poses a significant threat to human health. Despite considerable advancements in immunotherapy for GC, the effectiveness of current immunotherapeutic targets remains constrained by the heterogeneity of the tumor microenvironment and mechanisms of immune evasion. Consequently, the identification of novel immunotherapy targets has emerged as a critical area of research. This study investigates the potential of Pygo2 as a target for immunotherapy in GC.The expression and cell localization of Pygo2 in GC tissues were characterized by single cell sequencing, flow cytometry and mIHC. The relationship among Pygo2 expression and prognosis, immune microenvironment and immunotherapy effect was studied in 282 gastric cancer patients.The findings indicate a significant upregulation of Pygo2 expression in GC tissues, particularly within tumor cells and T cells. Pygo2 expression in T cells is not only correlated with the advanced T stage and N stage but also inversely associated with patient survival. Additionally, overexpression of T cell Pygo2 resulted in a significant increase in TCF7, which suggested Pygo2 + T cells might represent a subset of exhausted T cells. The study also demonstrated that the density of Pygo2 + CD8 + T cells is negatively correlated with the efficacy of immunotherapy.Tumor-infiltrating Pygo2 + T cells could be applied as a clinical prognosticator and a predictive biomarker for immunotherapy responsiveness to GC. These findings offer new therapeutic targets for the treatment of GC and provide fresh insights into cancer treatment strategies.
Keywords: gastric cancer, immunotherapeutic response, Pygo2, single-cell sequencing, immune microenvironment
Received: 19 Mar 2025; Accepted: 01 Jul 2025.
Copyright: © 2025 Weilong, Yan, Zhang, sang, Bu, Deng, Li, Li, Fu and Cui. 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:
Jiajing Li, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China
Yang Fu, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China
Jinyuan Cui, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China
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