Neutrophils are important in inflammation, but their contribution to tumorigenesis has remained unclear. In Nature, Wculek and Malanchi show that neutrophils are the main drivers of metastatic invasion of the lungs in a mouse model of breast cancer. CD11b+Ly6G+ neutrophils are present at low frequencies in the primary tumors, but they accumulate in the pre-metastatic lung before infiltration by cancer cells, and their numbers increase in the metastatic lung. Genetic, conditional or antibody-mediated depletion of neutrophils at the pre-metastatic stage diminishes metastatic progression with no effect on the primary tumors. Pre-metastatic lung neutrophils isolated ex vivo and neutrophil-derived leukotriene mediators enhance the metastatic initiation potential of cancer cells, possibly by providing a proliferative advantage to highly tumorigenic cells. Genetic or pharmacological deletion of leukotrienes diminishes spontaneous lung metastasis in mice.

Nature (9 December 2015) doi:10.1038/nature16140