Liver metastases license neutrophils through IL-1 to potentiate cancer progression.

Abstract

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 manner. Thus, liver metastasis rewires systemic immunity to promote cancer progression. This work has implications for treatment strategies to address the poor clinical outcomes associated with liver metastasis.