Figure 2. . Tumor-derived exosomes in the tumor microenvironment carry and deliver both immunoinhibitory (protumor) and immunostimulatory (antitumor) signals to immune cells.

Immune cells that recognize the inhibitory and stimulatory signals on the TEX surface engage TEX in a cross-talk that leads to the TEX uptake and transfer of mRNA, miRNAs and proteins from TEX to recipient cells. Molecular signals and nucleic acids delivered by TEX induce reprogramming of recipient cell functions via molecular/genetic mechanisms discussed in the text. Antitumor activities of most immune cells are blocked (black arrows), while the regulatory immune cells (Treg and Breg, MDSC) are stimulated by TEX to expand and acquire protumor suppressor functions. TEX also carry MHC molecules, tumor associated antigens and costimulatory molecules and thus can stimulate immune cells to upregulate antitumor activities (red arrows), including enhanced maturation of DCs and enhanced tumor antigen processing. Cross-talk of these DC with T and B cells leads to their activation. NK cells can be activated by soluble factors delivered by TEX. The TEX-immune cell cross-talk provides contextual reprogramming which in the TME is heavily biased toward immune suppression.

DC: Dendritic cell; MDSC: Myeloid-derived suppressor cell; MHC: Major histocompatibility complex; NK: Natural killer; TEX: Tumor-derived exosomes; TME: Tumor microenvironment.