Dual roles of neutrophil extracellular traps in tumors: From pro‑metastatic mechanisms to immunotherapeutic strategies (Review)

Neutrophil extracellular traps (NETs) serve a dual role in tumor progression. On the one hand, they promote tumor invasion and metastasis by facilitating cancer cell adhesion to the endothelium, supporting vascular remodeling and establishing pre-metastatic niches. On the other hand, NETs exert potent immunosuppressive effects that foster tumor immune evasion and contribute to immunotherapy resistance. Specifically, NETs create physical barriers within the tumor microenvironment, directly suppress effector immune cells, and degrade critical molecules such as interferon-γ, leading to immune exhaustion and dysfunction. The present review comprehensively summarizes the biology of NETs and their molecular mechanisms in tumor metastasis, with a particular focus on NET-mediated immunosuppression and its causal link to immunotherapy resistance. This review further discusses emerging strategies that disrupt NET formation or function, which may reverse their immunosuppressive impact and restore antitumor immunity, thereby enhancing the efficacy of current immunotherapies.