NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps

Neutrophils are major effectors and regulators of the immune system. They play critical roles not only in the eradication of pathogens but also in cancer initiation and progression. Conversely, the presence of cancer affects neutrophil activity, maturation, and lifespan. By promoting or repressing key neutrophil functions, cancer cells co-opt neutrophil biology to their advantage. This co-opting includes hijacking one of neutrophils' most striking pathogen defense mechanisms: the formation of neutrophil extracellular traps (NETs). NETs are web-like filamentous extracellular structures of DNA, histones, and cytotoxic granule-derived proteins. Here, we discuss the bidirectional interplay by which cancer stimulates NET for-mation, and NETs in turn support disease progression. We review how vascular dysfunction and throm-bosis caused by neutrophils and NETs underlie an elevated risk of death from cardiovascular events in cancer patients. Finally, we propose therapeutic strategies that may be effective in targeting NETs in the clinical setting.

Automated summary

Neutrophils are key players in the immune system, involved in pathogen eradication and cancer progression. Cancer cells manipulate neutrophil biology, including the formation of neutrophil extracellular traps (NETs), to their advantage. This article discusses how cancer stimulates NET formation and how NETs contribute to disease progression. It also explores the link between neutrophils, NETs, vascular dysfunction, thrombosis, and increased cardiovascular risk in cancer patients. Therapeutic strategies targeting NETs in clinical settings are proposed.