The crosstalk between inflammation and tumorigenesis is now clearly established. However, how inflammation is elicited in the metastatic environment and the corresponding contribution of innate immunity pathways in suppressing tumor growth at secondary sites are poorly understood. Here, we show that mice deficient in Nlrp3 inflammasome components had exacerbated colorectal cancer metastatic growth in the liver, which was mediated by impaired IL-18 signaling. Control of tumor growth was independent of differential cancer cell colonization or proliferation, intestinal microbiota effects or tumoricidal activity by the adaptive immune system. Instead, the inflammasome-IL-18 pathway impacted maturation of hepatic NK cells, surface expression of FasL and capacity to kill FasL-sensitive tumors. Our results define a regulatory signaling circuit within the innate immune system linking inflammasome activation to effective NK cell-mediated tumor attack that is required to suppress colorectal cancer growth in the liver.
