Macrophage Inflammasome Activation in Breast Cancer

Breast cancer progression is promoted by local inflammation. Indeed, inflammatory cytokinesand immune infiltration are independent prognosis markers of breast cancer progression. However, the mechanisms underlying the interplay between inflammasome, pro-inflammatory cytokines and tumor progression remain to be fully understood. Our early observations highlighted a potential role of inflammasome activation in cancer-associated macrophages in both local inflammation and tumor growth. Here, we specifically assessed macrophage NLRP3 inflammasome activation, pro-inflammatory cytokine secretions and phagocytosis triggered by tumor cells. Through in vitro assessments, our data indicates that activation of macrophages by tumor cell secretions was associated with promotion of inflammasome especially NLPR3 inflammasome activation, and pro-inflammatory IL-1ß and IL-18 cytokine secretions. Indeed, following incubation with tumor secretions, macrophage phenotype and phagocytic activities were significantly altered. Moreover, incubation with the NLRP3 inflammasome specific inhibitor, MCC950 reduced both the expression and secretion of pro-inflammatory cytokines with some effects on phenotype and phagocytosis of inflammasome-activated macrophages. Taken together our data suggest that breast tumor cell secretions promote inflammasome activation and secretion of pro-inflammatory cytokines in macrophages in vitro and that inflammasome activation promotes a pro-tumorigenic phenotype in macrophages favoring breast cancer growth and metastasis. Future investigations will further those observations and assess the potential of targeting those pathways in macrophages to prevent breast cancer progression.