Fig. 3

Neutrophils and NETs in cancer. A Neutrophils exert their effect in a cytolytic way. Neutrophils extravasate upon MET receptor upregulation, and HGF triggers nitric oxide release to induce cell death in melanoma cells. Hydrogen peroxide (H₂O₂) allows cytotoxic Ca²⁺ influx via TRPM2 into breast cancer cells. Neutrophils promote detachment of the basement membrane to make oxygen inaccessible in uterine cancer cells. IFNγ upregulates TRAIL in neutrophils to induce apoptosis in leukemic T cells. IL-1β by neutrophils induces upregulation of ZEB1 (EMT marker) to induce a phenotype switch. B Tumor cells may release cytokines or extracellular vesicles (EV) to activate neutrophils. In turn, effectors such as ROS or NETs are released to promote tumor growth. C Evidence in melanoma supports a proliferation-promoting role of NETs, impeding invasiveness and cell viability. Other tumor types suggest an invasive phenotype upon NET release (created with BioRender.com)