miR-182 targeting reprograms tumor-associated macrophages and limits breast cancer progression

Significance Breast cancer is a major threat of women’s health worldwide. Nontumor cell components play crucial roles in cancer. Macrophages, the cells of the innate immune system that normally exert antitumor activities, can be educated by tumors to an alternatively activated phenotype that is known to promote tumor progression. Understanding the mechanism of macrophage education by tumor cells will help the design of new therapeutic approaches. We find that breast tumor cells induce the expression of a microRNA, miR-182, in macrophages, and miR-182 promotes macrophage alternative activation to drive tumor development. Importantly, using cationized mannan-modified extracellular vesicles to load miR-182 inhibitors and deliver the inhibitors specifically into macrophages can effectively inhibit alternative activation of macrophages and suppress breast tumor development.