Qin Yansong, Liu Yunmei, Dong Peixin, Zou Wen-Bin, Li Zhaoshen, Huang Lei
Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, The First Affiliated Hospital of Naval Medical University/Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
School of Cultural Heritage and Information Management, Shanghai University, Shanghai, China.
Cell Mol Biol Lett. 2025 Jun 16;30(1):71. doi: 10.1186/s11658-025-00744-4.
Gastric cancer (GC) is a significant challenge for global health. Neutrophils, the predominant white blood cells in the innate immune system, are increasingly becoming known as potential contributors to either tumor-promoting or tumor-suppressive activities within different tumor biology settings. This review highlights such dual roles of neutrophils in GC, where complex interactions occur within the tumor microenvironment. Specifically, we focus on the formation and function of neutrophil extracellular traps (NETs), which have emerged as critical players in GC progression. NETs influence key processes such as inflammation, angiogenesis, and metastasis. This review offers a comprehensive analysis of the polarization of neutrophils into two of its distinct subtypes, namely N1 and N2, which exert opposing influences on tumor biology. While N1 neutrophils exert anti-tumor properties, N2 neutrophils are generally regarded as pro-tumor. We uniquely discuss how these subtypes interact with cancer cells, affecting epithelial-mesenchymal transition and immune evasion mechanisms. These interactions change the tumor microenvironment and impact overall GC progression. In addition, we underscore the potential of neutrophils and their associated molecules as biomarkers and therapeutic targets. Specific neutrophil-derived markers and neutrophil-associated signaling pathways, along with their perspectives in personalized medicine that would pave the way for neutrophil-based anti-GC therapy, have been discussed in this review. Through the integration of these perspectives, we aim to guide future research involving neutrophils and their therapeutic implications, thus establishing strategies to precisely and effectively treat GC and improve prognosis.
胃癌（GC）是全球健康面临的重大挑战。中性粒细胞是固有免疫系统中主要的白细胞，在不同的肿瘤生物学环境中，越来越被认为是肿瘤促进或肿瘤抑制活动的潜在贡献者。本综述强调了中性粒细胞在胃癌中的这种双重作用，其中在肿瘤微环境中发生了复杂的相互作用。具体而言，我们关注中性粒细胞胞外陷阱（NETs）的形成和功能，其已成为胃癌进展的关键因素。NETs影响炎症、血管生成和转移等关键过程。本综述全面分析了中性粒细胞向其两种不同亚型（即N1和N2）的极化，这两种亚型对肿瘤生物学产生相反的影响。虽然N1中性粒细胞具有抗肿瘤特性，但N2中性粒细胞通常被认为是促肿瘤的。我们独特地讨论了这些亚型如何与癌细胞相互作用，影响上皮-间质转化和免疫逃逸机制。这些相互作用改变了肿瘤微环境并影响了胃癌的整体进展。此外，我们强调了中性粒细胞及其相关分子作为生物标志物和治疗靶点的潜力。本综述讨论了特定的中性粒细胞衍生标志物和中性粒细胞相关信号通路，以及它们在个性化医学中的前景，这将为基于中性粒细胞的抗胃癌治疗铺平道路。通过整合这些观点，我们旨在指导未来涉及中性粒细胞及其治疗意义的研究，从而制定精确有效地治疗胃癌并改善预后的策略。
