Neutrophil extracellular traps: the hidden driver of gastrointestinal cancer and emerging therapeutic strategies

As the most abundant subset of leukocytes in the innate immune system, neutrophils are central to host defense, particularly against bacterial and fungal infections. With advances in tumor microenvironment (TME) research, their multifunctional roles in tumor biology have been clarified, and the identification of neutrophil extracellular traps (NETs) has provided a novel perspective for understanding neutrophil-mediated regulation of tumor initiation, progression, and metastasis. NETs are reticular structures of chromatin fibers released by activated neutrophils, comprising DNA backbones, histones, and various antimicrobial proteins, initially recognized as an antibacterial defense mechanism. However, recent studies reveal NETs exert a dual role in tumor progression: directly promoting metastasis by enhancing tumor cell migration, trapping circulating tumor cells (CTCs), reactivating dormant cancer cells, and increasing vascular permeability, while also reshaping the TME to support pre-metastatic niche formation. This review systematically summarizes the molecular mechanisms of NETs in gastrointestinal tumor initiation, progression, and metastasis, and explores potential NETs-targeted anti-tumor therapeutic strategies, aiming to provide a theoretical basis for novel gastrointestinal tumor treatment directions.