The anti-tumor effect of extracellular vesicles derived from cytokine-activated CD8+ T cells.

ABSTRACT

Extracellular vesicles (EVs) are the nano-sized membrane particles secreted by various cell types, which are involved in many important cellular processes. Recently, EVs originating from immune cells, such as dendritic cells, chimeric antigen receptor T cells (CAR-T) and natural killer cells, have attracted much attention because of their known direct and indirect antitumor activity. Here, we report the EVs released by cytokine-activated CD8 + T cells (caCD8) and its cytotoxicity against cancer cells. CaCD8 cells can release EVs following stimulation of CD8+ T cells with an anti-CD3 antibody and a cytokines cocktail ex vivo. The isolated vesicles have typical EV characteristics, such as an oval shape and a size distribution between 30-200 nm, as well as CD81 expression. Notably, caCD8-EVs displayed cytotoxicity against various cancer cells in vitro. Furthermore, mechanism analysis demonstrates that caCD8-EVs not only contain typical cytotoxic proteins (i.e., granzyme B and perforin), but also significantly enrich IFNγ compared to caCD8 cells. The EVs-derived IFNγ participates in EVs-induced apoptosis in cancer cells. Therefore, our data reveal an antitumor effects of EVs secreted from caCD8 cells and the potential role of the EVs-derived IFNγ.