Fig. 1: Neutrophil extracellular traps in cancer.

Neutrophils originating from bone marrow have a short lifespan in circulation, which is controlled by programmed cell death. When attracted by chemokines, they extravasate into tumor tissue where they are activated to delay apoptosis and engage in the inflammatory tumor microenvironment. A fraction of activated neutrophils may reverse migrate and home back to the bone marrow which shapes further neutrophil release. The tumor-invading neutrophils are exposed to hypoxia as well as cancer and stroma cell signals, which can trigger the formation of neutrophil extracellular traps (NETs). NET components such as oxidized DNA may stimulate an inflammatory response by macrophages or dendritic cells. NET-associated proteases alter the extracellular matrix and NET-derived HMGB1 molecules activate cancer cells to jointly promote tumor cell proliferation, migration, invasion, and metastasis.