Roles of neutrophils in gastric carcinogenesis and progression: mechanisms, therapeutic potential, and clinical translational prospects_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HE Jiarui , QIN Long , CAI Weiwen ,  JIAO Zuoyi

Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou 730030, P. R. China;

Corresponding?author：

JIAO Zuoyi, Email: jiaozy@lzu.edu.cn

Keywords：

gastric cancer; neutrophils; tumor immune microenvironment; targeted therapy

DOI：

10.7507/1007-9424.202606050

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically summarize the dynamic changes, mechanisms of action, and potential clinical translational value of neutrophils during gastric carcinogenesis and progression, thereby providing a reference for understanding the gastric cancer immune microenvironment and exploring therapeutic interventions. Method Recent basic and clinical studies and relevant reviews were summarized and analyzed, with a focus on the Correa cascade of gastric carcinogenesis, neutrophil functional plasticity, and targeted interventions. Results The Correa cascade of gastric carcinogenesis is typically accompanied by dynamic remodeling of the inflammatory microenvironment and immune cell composition. Neutrophils exhibit characteristic functional changes across the cascade. During chronic non-atrophic gastritis, they predominantly display an inflammatory phenotype and exert dual effects involving antimicrobial defense and mucosal injury. During atrophic gastritis, intestinal metaplasia, and dysplasia, neutrophil infiltration persists, although their functional states remain unclear. At the gastric cancer stage, neutrophils evolve into highly heterogeneous tumor-associated neutrophils (TANs) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which contribute to tumor progression, immune evasion, and metastasis through multiple mechanisms involving chemokine axes, immunosuppressive molecules, extracellular matrix remodeling, and neutrophil extracellular traps (NETs). The principal neutrophil-targeted strategies include blocking neutrophil recruitment to the tumor microenvironment, modulating N1/N2 polarization, interfering with NETs formation and function, and alleviating PMN-MDSC-mediated myeloid immunosuppression. These strategies have shown potential to enhance antitumor immunity and improve the efficacy of immune checkpoint inhibitors in preclinical models of gastric cancer; however, no therapy directed solely at neutrophils has yet been approved for clinical use in gastric cancer. Conclusion The dynamic evolution and marked functional heterogeneity of neutrophils in gastric cancer provide potential targets for combination immunotherapy; nevertheless, clinical translation demands precise subtyping of neutrophils, selective intervention, and prospective validation anchored in the Correa cascade.

Citation： HE Jiarui, QIN Long, CAI Weiwen, JIAO Zuoyi. Roles of neutrophils in gastric carcinogenesis and progression: mechanisms, therapeutic potential, and clinical translational prospects. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(9): 1271-1279. doi: 10.7507/1007-9424.202606050 Copy

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59.
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76. Deshpande NU, Bianchi A, Amirian H, et al. Cell-specific nanoengineering strategy to disrupt tolerogenic signaling from myeloid-derived suppressor cells and invigorate antitumor immunity in pancreatic cancer [J/OL]. Cancer Immunol Immunother, 2025, 74(8): 247. doi: 10.1007/s00262-025-04096-y.

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Roles of neutrophils in gastric carcinogenesis and progression: mechanisms, therapeutic potential, and clinical translational prospects

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