Liver metastases license neutrophils throygh IL-1 to potentiate cancer progression
Liver metastases are associated with poor cancer outcomes in many solid malignancies, but the factors influencing the trajectory of patients with liver metastases are poorly defined. It is known that liver metastases suppress systemic antitumor immunity; however, the underlying mechanisms remain incompletely described. We report that liver metastases promote disease progression in patients and preclinical models. Patients with liver metastases progress rapidly, regardless of primary tumor type. In multiple murine models, we find that liver metastases potentiate neutrophil migration and activity. Neutrophils licensed by liver metastasis augment metastatic colonization in an IL-1 dependent fashion. Thus, liver metastasis rewires systemic immunity to promote cancer progression. This work has  implications for novel treatment strategies to address the poor clinical outcomes associated with liver metastasis. Overall design: Black6 mice were inoculated with B16F10 subcutaneous tumors, and either received B16F10 liver metastases or a sham injection. The lungs and blood of these mice were harvested. CD45+ StemCell kits were used to enrich immune cells.