Tumors exploit CXCR4 <sup>hi</sup> CD62L <sup>lo</sup> aged neutrophils to facilitate metastatic spread
Zhenzi Peng, Cuiwei Liu, Aaron Victor, Duo‐Yao Cao, Luciana C. Veiras, Ellen A. Bernstein, Zakir Khan, Jorge F. Giani, Xiaojiang Cui, Kenneth E. Bernstein, Derick Okwan‐Duodu
Abstract
naive neutrophils, aged neutrophils more robustly promote tumor migration and support metastasis through the increased release of several metastasis-promoting factors, including neutrophil extracellular traps (NETs), reactive oxygen species, vascular endothelial growth factors, and metalloproteinases (MMP-9). Adoptive transfer of aged neutrophils significantly enhanced metastasis of breast (4T1) and melanoma (B16LS9) cancer cells to the liver, and these effects were predominantly mediated by NETs. Our results highlight that in addition to modulating MDSC production, targeting aged neutrophil clearance and homeostasis may be effective in reducing cancer metastasis.