Neutrophil extracellular traps in cancer

Within the tumour immune microenvironment (TIME), neutrophils can undergo NETosis to release neutrophil extracellular traps (NETs), which are protein-decorated DNA webs that promote cancer progression, metastasis and immune evasion. NETs promote cancer progression by fostering an immunosuppressive, pre-metastatic niche in regional lymph nodes prior to overt metastasis. Anticancer therapies such as immune checkpoint inhibitors, chemotherapy and radiation therapy can induce the formation of NETs, which can facilitate subsequent cancer invasion, migration, metastasis and recurrence through several mechanisms that dampen antitumour immune responses and sequester neoplastic cells. Precision blood and tumour testing for the NET burden could inform both patient prognosis as well as eligibility for treatments aimed at targeting NETosis, NETs and/or neutrophils. The importance of staging with other patient and treatment factors will thus inform the design of clinical trials evaluating NET-directed therapies. In this Review, we highlight our recent understandings of NET biology in cancer, and emphasize the translational data available, as well as the need for further clinical trials evaluating NETs and NET-directed therapies.