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JMG, Animals, Cell Line, Tumor, Coculture Techniques, Disease Models, Animal, Female, Granulocyte Colony-Stimulating Factor, Humans, Injections, Intravenous, Killer Cells, Natural, Lung, Lung Neoplasms, Mammary Glands, Animal, Mammary Neoplasms, Animal, Mice, Mice, Inbred NOD, Neutropenia, Neutrophils, Primary Cell Culture

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Nat Commun 2020 Sep 1; 11(1):4387





CA034196, OD026440, AI132963, Pyewacket Fund


The role of neutrophils in solid tumor metastasis remains largely controversial. In preclinical models of solid tumors, both pro-metastatic and anti-metastatic effects of neutrophils have been reported. In this study, using mouse models of breast cancer, we demonstrate that the metastasis-modulating effects of neutrophils are dictated by the status of host natural killer (NK) cells. In NK cell-deficient mice, granulocyte colony-stimulating factor-expanded neutrophils show an inhibitory effect on the metastatic colonization of breast tumor cells in the lung. In contrast, in NK cell-competent mice, neutrophils facilitate metastatic colonization in the same tumor models. In an ex vivo neutrophil-NK cell-tumor cell tri-cell co-culture system, neutrophils are shown to potentially suppress the tumoricidal activity of NK cells, while neutrophils themselves are tumoricidal. Intriguingly, these two modulatory effects by neutrophils are both mediated by reactive oxygen species. Collectively, the absence or presence of NK cells, governs the net tumor-modulatory effects of neutrophils.


We appreciate Dr. Kevin Seburn for his critical editing of the manuscript and also thank the assistance from The Jackson Laboratory Scientific Service.

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