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

Jose M. Adrover, Sheri A.C. McDowell, Xue Yan He, Daniela F. Quail, Mikala Egeblad

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations

Abstract

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 formation, and NETs in turn support disease progression. We review how vascular dysfunction and thrombosis 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.

Original languageEnglish
Pages (from-to)505-526
Number of pages22
JournalCancer Cell
Volume41
Issue number3
DOIs
StatePublished - Mar 13 2023

Keywords

  • cancer
  • metastasis
  • NETs
  • neutrophil extracellular traps
  • neutrophils
  • tumor

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