Yao ZY, Ma LJ, Han ZX, Ji GJ. Evolving landscape of the gastric cancer immune microenvironment: From spatial architecture to precision biomarkers. World J Gastrointest Oncol 2026; 18(6): 119114 [DOI: 10.4251/wjgo.v18.i6.119114]
Corresponding Author of This Article
Gui-Juan Ji, PhD, Professor, Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Xuzhou 221000, Jiangsu Province, China. 190621642@qq.com
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Oncology
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review-article
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Yao ZY, Ma LJ, Han ZX, Ji GJ. Evolving landscape of the gastric cancer immune microenvironment: From spatial architecture to precision biomarkers. World J Gastrointest Oncol 2026; 18(6): 119114 [DOI: 10.4251/wjgo.v18.i6.119114]
World J Gastrointest Oncol. Jun 15, 2026; 18(6): 119114 Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.119114
Evolving landscape of the gastric cancer immune microenvironment: From spatial architecture to precision biomarkers
Zhi-Yuan Yao, Li-Jie Ma, Zheng-Xiang Han, Gui-Juan Ji
Zhi-Yuan Yao, Zheng-Xiang Han, Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
Li-Jie Ma, The First Clinical College of Xuzhou Medical University, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
Gui-Juan Ji, Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
Co-first authors: Zhi-Yuan Yao and Li-Jie Ma.
Co-corresponding authors: Zheng-Xiang Han and Gui-Juan Ji.
Author contributions: Yao ZY validated and visualized the manuscript, validated and revised the manuscript; Ma LJ wrote and visualized the original draft; Yao ZY and Ma LJ contributed equally to this manuscript as co-first authors; Han ZX designed and revised the original draft; Ji GJ designed and edited the manuscript; Han ZX and Ji GJ contributed equally to this manuscript as co-corresponding authors; all authors read and approved the final manuscript.
AI contribution statement: We use ChatGPT solely for language translation and polishing, and we have engaged a professional language polishing agency to handle the subsequent refinement. Artificial intelligence merely serves to refine language and does not perform automatic generation. Artificial intelligence was employed for language polishing, translation, and framework drafting assistance, but not for data analysis. Artificial intelligence tools were not involved in the design of the research or the interpretation of the results. Any images in the manuscript are not generated by artificial intelligence.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Gui-Juan Ji, PhD, Professor, Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Xuzhou 221000, Jiangsu Province, China. 190621642@qq.com
Received: January 21, 2026 Revised: February 5, 2026 Accepted: March 5, 2026 Published online: June 15, 2026 Processing time: 140 Days and 22.7 Hours
Abstract
Gastric cancer remains a paradigm of therapeutic recalcitrance, driven by a complex ecosystem where therapeutic efficacy is dictated by the dynamic interplay between genomic instability and the tumor immune microenvironment. While biomarkers such as programmed death-ligand 1 expression and microsatellite instability currently guide therapeutic decisions, they offer only a static glimpse into a spatially and temporally evolving landscape. In this mini-review, we systematically delineate the co-evolution of spatial architecture, metabolic rewiring, and microbial interactions that orchestrate immune evasion in gastric cancer. We dissect how specific “cellular neighborhoods” – governed by the interplay between myofibroblastic cancer-associated fibroblasts and intratumoral microbiota like Fusobacterium nucleatum – construct physical and biological barriers to T-cell infiltration. Furthermore, we explore “invisible“ drivers of resistance, highlighting the synergistic potential of ferroptosis and pyroptosis in reshaping immunogenicity and the emerging role of the neuro-immune axis. Finally, we evaluate the clinical utility of next-generation biomarkers, ranging from tertiary lymphoid structure maturity and circulating tumor DNA molecular kinetics to artificial intelligence-driven “digital twins”. By integrating these multi-dimensional insights, we propose a strategic framework for precision immuno-oncology, transitioning from static profiling to holistic ecosystem engineering.
Core Tip: Gastric cancer therapy must evolve beyond traditional approaches by focusing on the tumor immune microenvironment, which is shaped by spatial architecture, metabolic reprogramming, and microbiota interactions. The reliance on static biomarkers like programmed death-ligand 1 expression is shifting towards dynamic markers, such as tertiary lymphoid structure and circulating tumor DNA, to better predict treatment outcomes. A shift towards “ecosystem engineering” strategies, including vascular normalization, stromal reprogramming, and combination therapies like antibody-drug conjugates and chimeric antigen receptor T cells, is crucial for overcoming immune evasion and improving patient responses.
