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Neutrophil extracellular traps (NETs) are fibrous web-like structures composed of decondensed chromatin and granular proteins released by neutrophils, with the ability to capture and kill bacteria. Pathogens, such as bacteria and viruses, can trigger the formation of NETs via NETosis, a type of programmed cell death that has two distinct forms: suicidal NETosis and vital NETosis. Numerous studies have found that NETs interact with immune cells in the tumor microenvironment, where they activate macrophages, promote immunosuppressive effects of myeloid-derived suppressor cells, and coat the tumor surface to prevent cytotoxic effects of CD8+ T cells and natural killer cells. Recent research has identified a substantial presence of NETs in oral squamous cell carcinoma (OSCC) tissues, indicating a complex relationship between NETs and OSCC development. Depending on the phenotype of neutrophils, NETs may exhibit pro-tumor or anti-tumor effects. For instance, NETs derived from N1-type neutrophils may exert anti-tumor effects, while TGF-β-induced NETs derived from N2-type neutrophils may exert pro-carcinogenic activity, thereby contributing to the development of oral squamous metaplasia. Furthermore, NETs likely play a role in OSCC metastasis by capturing circulating tumor cells and inducing a hypercoagulable state, thereby facilitating tumor-related thrombus formation and hematogenous metastasis. The involvement of NETs in the occurrence and progression of OSCC opens new avenues for anti-tumor therapy and prognostication. Inhibiting NET formation can significantly suppress the development of chemotherapy-induced drug resistance and reduce the risk of thrombosis in OSCC patients, thereby inhibiting tumor metastasis. Currently, multiple prognostic models based on NET-related genes have been constructed and validated for head and neck squamous cell carcinoma, indicating the potential clinical value of NETs. However, the association between NETs and OSCC treatment is still unclear, necessitating further research on its underlying mechanisms and feasibility. This article attempts to review the relationship between NETs and OSCC, aiming to provide novel perspectives for OSCC treatment. |
