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Extracellular DNA (eDNA) is the primary structural component of Neutrophil Extracellular Traps (NETs), which are web-like chromatin structures decorated with antimicrobial proteins (Park et al., 2016, Science Translational Medicine). While NETs are essential for trapping and killing pathogens during innate immune responses, their presence in the tumor microenvironment (TME) is associated with poor prognosis and cancer progression (Cools-Lartigue et al., 2013, Journal of Clinical Investigation). In the TME, eDNA scaffolds act as a physical barrier that protects tumor cells from immune-mediated killing by T cells and Natural Killer cells (Teijeira et al., 2020, Immunity). Furthermore, eDNA can trap circulating tumor cells, facilitating their adhesion to distant vascular beds and promoting metastatic colonization (Albrengues et al., 2018, Science). Therapeutic targeting of eDNA primarily involves the use of nucleases like Dornase alfa to digest the DNA backbone, thereby dismantling the NET structure and sensitizing tumors to immunotherapy or chemotherapy.
Enzymatic degradation of the phosphodiester backbone of extracellular DNA strands, leading to the dissolution of the structural framework of neutrophil extracellular traps (NETs).
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