Tumor Entrained Neutrophils Inhibit Seeding in the Premetastatic Lung

SummaryPrimary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells. Here we demonstrate that neutrophils accumulate in the lung prior to the arrival of metastatic cells in mouse models of breast cancer. Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H2O2 and tumor secreted CCL2 is a critical mediator of optimal antimetastatic entrainment of G-CSF-stimulated neutrophils. TENs are present in the peripheral blood of breast cancer patients prior to surgical resection but not in healthy individuals. Thus, whereas tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site.

► Tumor entrained neutrophils (TENs) accumulate in the premetastatic lung
► TENs provide antimetastatic protection by eliminating disseminated tumor cells
► Tumor-secreted factors are both required and sufficient for neutrophil entrainment
► Tumor-secreted TGF-β protects the primary tumor from neutrophil cytotoxicity