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Zhang D, Li SH, Zhang WH, Weng J, Li ZH, Bai KH. Helicobacter pylori status in gastric cancer immunotherapy: Conflicting clinical associations, immune-microbial mechanisms, and biomarker challenges. World J Gastrointest Oncol 2026; 18(12): 126418 [DOI: 10.4251/wjgo.126418]
World J Gastrointest Oncol. Dec 15, 2026; 18(12): 126418 Published online Dec 15, 2026. doi: 10.4251/wjgo.126418
Helicobacter pylori status in gastric cancer immunotherapy: Conflicting clinical associations, immune-microbial mechanisms, and biomarker challenges
Di Zhang, Shu-Han Li, Wei-Hao Zhang, Jun Weng, Ze-Hua Li, Kun-Hao Bai
Di Zhang, School of Nursing, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Shu-Han Li, Institute of Transfusion, Chinese Academy of Medical Sciences, Chengdu 610052, Sichuan Province, China
Wei-Hao Zhang, Jun Weng, Ze-Hua Li, Kun-Hao Bai, Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, Guangdong Province, China
Co-first authors: Di Zhang and Shu-Han Li.
Co-corresponding authors: Ze-Hua Li and Kun-Hao Bai.
Author contributions: Zhang D and Li SH contributed to the literature search, data curation, formal analysis, and the writing including original draft preparation and subsequent review and editing as co-first authors; Zhang WH and Weng J were responsible for the visualization, including the design and production of all figures and tables; Li ZH and Bai KH designed the research, provided research support and revised the manuscript as co-corresponding authors; all authors read and approved the final manuscript.
AI contribution statement: Generative AI was used solely for language editing and polishing of the manuscript. It was not involved in the study design, literature search, study selection, data extraction, evidence synthesis, interpretation of findings, or preparation of scientific conclusions. All AI-assisted edits were carefully reviewed and verified by the authors for accuracy, appropriateness, and consistency with the underlying evidence. The authors take full responsibility for the accuracy, integrity, and content of the final manuscript.
Supported by National Natural Science Foundation of China, No. 82403973.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Kun-Hao Bai, MD, PhD, Associate Chief Physician, Associate Professor, Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, No. 651 Dongfengdong Street, Yuexiu District, Guangzhou 510060, Guangdong Province, China. baikh@sysucc.org.cn
Received: August 4, 2026 Revised: August 14, 2026 Accepted: October 16, 2026 Published online: December 15, 2026 Processing time: 98 Days and 9.8 Hours
Abstract
Immune checkpoint inhibitors (ICIs) have become an important treatment option for gastric cancer, but therapeutic responses remain highly heterogeneous. Helicobacter pylori (H. pylori), a major risk factor for gastric carcinogenesis, may continue to influence tumor immunity and immunotherapy outcomes after cancer develops. However, current clinical findings are inconsistent, and the biomarker value of H. pylori remains uncertain. This review critically summarizes the clinical and mechanistic evidence linking H. pylori status to ICI outcomes in gastric cancer. Potential mechanisms include regulation of programmed cell death protein 1/programmed death-ligand 1 signaling, T-cell function, antigen presentation, myeloid immunosuppression, and microbial ecology. The divergent clinical results may reflect differences in infection status, detection methods, tumor molecular subtypes, disease stage, treatment setting, and previous therapeutic exposures. Current evidence does not support H. pylori as a validated predictive biomarker for ICI response. Rather, it may represent a context-dependent indicator of the tumor-immune-microbial background. Prospective longitudinal studies with standardized definitions of current active infection, previous infection of uncertain current status, successfully eradicated infection, and no evidence of previous infection are needed to determine whether specific H. pylori-related biological states modify the relative benefit of immunotherapy.
Core Tip: Helicobacter pylori infection may influence gastric cancer immunotherapy outcomes, but clinical evidence remains conflicting – some studies associate positivity with poorer survival, others with enhanced benefit. This review examines the mechanistic pathways underlying this duality, including programmed cell death protein 1/programmed death-ligand 1 regulation, T-cell dysfunction, antigen presentation impairment, myeloid immunosuppression, and microbial ecological shifts. We propose that divergent findings reflect differences in infection definitions, detection methods, tumor subtypes, and treatment settings. Current evidence does not support Helicobacter pylori as a validated predictive biomarker; rather, it represents a context-dependent indicator of the tumor-immune-microbial background. Prospective studies with standardized infection definitions are critically needed.
