Fig. 3.

EV-mediated immune suppression. Three different mechanisms have been described thus far for how tumor-derived EVs silence anti-tumor immune responses. (1) EVs directly suppress innate and adaptive immune cell responses through interactions of cargo present at their surface, such as immune checkpoint ligands (e.g. PD-L1) and NKG2D ligands. (2) EVs can eliminate specific classes of immune cells through Fas ligand-mediated apoptosis. (3) EVs strongly promote pro-tumorigenic phenotypes in some immune cells, such as CD4⁺ T cells and CD14⁺ monocytes. In addition, coerced immune cells further support immune suppression by producing their own EVs for the secretion of immunosuppressive compounds. ADCC, antibody-dependent cell-mediated cytotoxicity.