Tumor-derived extracellular vesicles activate primary monocytes.

Tumor cells educate immune effector cells in their vicinity by releasing factors that manipulate their phenotype and function. In fact, the thus generated immunosuppressive tumor microenvironment constitutes an integral part and a hallmark of solid tumors and contributes significantly to tumor development and immune escape. It has long been thought that soluble factors like prostaglandin E2 and TGF-β are the main mediators of these effects. But tumor cells also constantly release large number of extracellular vesicles (EVs), which are important conveyors of immune responses. We show here that tumor-derived EVs interact with primary monocytes and induce an activated phenotype, which is also observed in tumor-associated macrophages. Thus, both tumor-derived EVs and soluble factors together collaborate to form the immunosuppressive milieu of the tumor environment.