Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines.

Abstract

Extracellular vesicles (EVs) play a crucial role in intercellular communication as vehicles for the transport of membrane and cytosolic proteins, lipids, and nucleic acids including different RNAs. Dendritic cells (DCs)-derived EVs (DEVs), albeit variably, express major histocompatibility complex (MHC)-peptide complexes and co-stimulatory molecules on their surface that enable the interaction with other immune cells such as CD8+ T cells, and other ligands that stimulate natural killer (NK) cells, thereby instructing tumor rejection, and counteracting immune-suppressive tumor microenvironment. Malignant cells oppose this effect by secreting EVs bearing a variety of molecules that block DCs function. For instance, tumor-derived EVs (TDEVs) can impair myeloid cell differentiation resulting in myeloid-derived suppressor cells (MDSCs) generation. Hence, the unique composition of EVs makes them suitable candidates for the development of new cancer treatment approaches including prophylactic vaccine targeting oncogenic pathogens, cancer vaccines, and cancer immunotherapeutics. We offer a perspective from both cell sides, DCs, and tumor cells, on how EVs regulate the antitumor immune response, and how this translates into promising therapeutic options by reviewing the latest advancement in DEV-based cancer therapeutics.