94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1551259
This article is part of the Research TopicImmune Checkpoints Regulatory Mechanisms and Immunotherapy Strategies in Gastrointestinal TumorsView all 7 articles
High expression of CXCL13 predicts a favorable response to immunotherapy by upregulating CXCR5+CD8+T cell infiltration in gastric cancer
Provisionally accepted- 1The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
- 2Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin, China
- 3Zhengzhou People's Hospital, Zhengzhou, 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
Identifying predictive biomarkers for immune checkpoint inhibitors (ICIs) treatment is critical for gastric cancer (GC) prognosis. C-X-C motif chemokine ligand 13 (CXCL13) plays an important role in immune regulation by binding exclusively to its receptor CXCR5. Yet, its role, underlying mechanisms, and prognostic significance in ICIs-treated GC patients remains controversial. This study investigated the clinical significance of CXCL13 and its potential immunomodulatory function in GC patients.A total of 144 GC patients from two cohorts who received a combination of chemotherapy and anti-PD-1 antibody were analyzed. The expression of CXCL13 was assessed using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay. Associations between CXCL13, CXCR5, CD8, and CD4 were assessed by IHC and immunofluorescence. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model. The treatment response of CXCL13 and anti-PD-1 antibody was investigated using a subcutaneous xenograft tumor mouse model. The results suggested that patients with high CXCL13 expression have prolonged survival. High CXCL13 expression exhibited increased infiltration of CXCR5+CD8+ T cells and was associated with better outcomes. The combined assessment of CXCL13, CXCR5, and CD8+T cells was an independent predictor of prognosis. Additionally, CXCR5 and CD8+T cells were enriched in tertiary lymphoid structures (TLSs), which conferred a prognostic benefit in the presence of high CXCL13 expression. CXCL13 in combination with anti-PD-1 therapy retarded tumor growth in vivo, resulting in increased infiltration of CXCR5+CD8+ T cells. This study identified CXCL13 as a prognostic factor in GC patients receiving ICIs therapy, emphasizing its critical role in the anti-tumor microenvironment via CXCR5+CD8+ T cells.
Keywords: gastric cancer, Immunotherapy, Prognosis markers, CXCL13, CXCR5
Received: 25 Dec 2024; Accepted: 14 Apr 2025.
Copyright: © 2025 Xu, Li, Ning, Lu, Sun, Bai, Qiao, DENG 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: Ying Liu, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
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.