The effect of tumor-derived exosomes on immune regulation and cancer immunotherapy.

Tumor-derived exosomes (TEX) carry both immunosuppressive and immunostimulatory receptor/ligands that in part mimic the profiles of the parent tumor cells. Operating as an intercellular communication system, TEX deliver protumor or antitumor signals to immune and nonimmune cells reprogramming their functions. Mechanisms responsible for cellular reprogramming include cell surface signaling and/or uptake of TEX by recipient cells. Once internalized, TEX transfer mRNA, miRNA and proteins that promote transcriptional/translational activities. TEX-mediated signaling is contextual and, in the tumor microenvironment, TEX largely mediate suppression. TEX may interfere with immune therapies either by sequestration of therapeutic antibodies or elimination of vaccine-induced or adoptively-transferred immune effector cells. TEX are emerging as an ubiquitous subcellular system regulating immune responses in patients with cancer.