MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1595070
This article is part of the Research TopicTLS Heterogeneity in the Tumor Microenvironment and Immunotherapy: Mechanistic Studies and Target ExplorationView all articles
Roles and Functions of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Gastric Cancer Progression
Provisionally accepted
- 1Department of Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221000, Jiangsu Province, China, Xuzhou, Jiangsu Province, China
- 2Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, Jiangsu Province, China, Suzhou, Liaoning Province, China
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Gastric cancer (GC), a leading cause of cancer mortality, exhibits profound molecular heterogeneity and immunosuppressive tumor microenvironment (TME) features that limit therapeutic efficacy. This review elucidates the dual roles of tertiary lymphoid structures (TLS) and tumor-infiltrating lymphocytes (TILs) in GC progression. TLS, ectopic lymphoid organs formed under chronic inflammation, correlate with improved survival and immunotherapy sensitivity by fostering effector T/B cell interactions and antigen presentation. Conversely, immunosuppressive TME components like regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) drive immune evasion via cytokine-mediated suppression and checkpoint activation (PD-1/PD-L1). CD8+ T cells exert context-dependent effects, with high infiltration reducing recurrence risk but paradoxically inducing exhaustion in PD-L1-rich microenvironments. Th17 and memory T cells further modulate disease through IL-17-driven angiogenesis and CD45RO+ immune memory dynamics. Multi-omics-based TLS scoring and combinatorial therapies emerge as promising strategies to overcome resistance.
Keywords: gastric cancer, tertiary lymphoid structures, Tumor-infiltrating lymphocytes, Tumor Microenvironment, immune checkpoint inhibitors, progression, biomarkers
Received: 17 Mar 2025; Accepted: 12 May 2025.
Copyright: © 2025 Yao, Li, Di, Pei, Fang, Liu and Han. 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:
Haonan Liu, Department of Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221000, Jiangsu Province, China, Xuzhou, Jiangsu Province, China
Zhengxiang Han, Department of Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221000, Jiangsu Province, China, Xuzhou, Jiangsu Province, China
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