Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

Extracellular DNA may serve as marker in liquid biopsies to determine individual diagnosis and prognosis in cancer patients. Cell death or active release from various cell types, including immune cells can result in the release of DNA into the extracellular milieu. Neutrophils are important components of the innate immune system, controlling pathogens through phagocytosis and/or the release of neutrophil extracellular traps (NETs). NETs also promote tumor progression and metastasis, by modulating angiogenesis, anti-tumor immunity, blood clotting and inflammation and providing a supportive niche for metastasizing cancer cells. Besides neutrophils, other immune cells such as eosinophils, dendritic cells, monocytes/macrophages, mast cells, basophils and lymphocytes can also form extracellular traps (ETs) during cancer progression, indicating possible multiple origins of extracellular DNA in cancer. In this review, we summarize the pathomechanisms of ET formation generated by different cell types, and analyze these processes in the context of cancer. We also critically discuss potential ET-inhibiting agents, which may open new therapeutic strategies for cancer prevention and treatment.

Automated summary

Extracellular DNA in liquid biopsies can be used as a marker for individual diagnosis and prognosis in cancer patients. Various immune cells, including neutrophils, can release DNA into the extracellular environment, promoting tumor progression and metastasis. This review summarizes the mechanisms of extracellular trap formation by different cell types and analyzes their role in cancer. Potential inhibitors of extracellular trap formation are also discussed, offering new therapeutic strategies for cancer prevention and treatment.