Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β

Abstract

AbstractDespite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunosuppression in tumor-infiltrating macrophages. Here, we further showed that lung cancer microparticles (L-MPs) induce macrophages to release a key proinflammatory cytokine, IL-1β, thus promoting lung cancer development. The underlying mechanism involves the activation of TLR3 and the NLRP3 inflammasome by L-MPs. More importantly, tyrosine kinase inhibitor treatment-induced L-MPs also induce human macrophages to release IL-1β, leading to a tumor-promoting effect in a humanized mouse model. These findings demonstrated that in addition to their anti-inflammatory effect, L-MPs induce a proinflammatory phenotype in tumor-infiltrating macrophages, promoting the development of inflammatory and immunosuppressive tumor microenvironments.