Tumor-associated neutrophils in gastric cancer: dual roles with promising prognostic and therapeutic potential

Despite the traditional view of neutrophils as primarily antibacterial cells, emerging evidence has highlighted their significant involvement in cancer progression and the modulation of the tumor microenvironment (TME). Tumor-associated neutrophils (TANs) have been recognized as key players in various malignancies, exerting both pro-tumorigenic and anti-tumorigenic effects that can ultimately influence disease outcomes. In gastric cancer (GC.), one of the most prevalent and lethal digestive system malignancies worldwide, TANs facilitate tumor progression through chronic inflammation, genomic instability, immunosuppression, angiogenesis, and metastasis. Their functional states exist along a continuum shaped by cytokines, microbial signals, exosomal transfer, and stromal interactions, resulting in context-dependent functions across disease stages and molecular subtypes. Elevated peripheral neutrophil-to-lymphocyte ratio (NLR) and specific TAN subsets are associated with adverse clinical outcomes in many cohorts, although protective associations have been observed in defined settings. This review synthesizes current knowledge on TAN origin, recruitment, phenotypic heterogeneity, and bidirectional crosstalk within the multicellular GC TME. It further evaluates their prognostic potential and examines emerging opportunities for therapeutic modulation. A deeper mechanistic understanding of TAN biology may support the development of neutrophil-directed strategies to overcome therapeutic resistance and improve outcomes in this heterogeneous malignancy.