Dendritic cell-derived exosomes elicit potent anti-tumor immune responses in vivo

Dendritic cells (DCs) are professional antigen presenting cells, involved in the priming of T cell-mediated immune responses. We now show that in addition to direct cell-cell contacts and to the production of various cytokines, DCs may also trigger T cell responses through the secretion of antigen presenting vesicles, called exosomes. Exosomes represent the internal vesicles of multivesicular endosomes, which are secreted after fusion of the external membrane of endosomes with the plasma membrane. Human and mouse DCs secrete exosomes bearing endosomal markers absent from the cell surface, such as CD63 and CD82. DC-derived exosomes also express MHC class II and B7.2 co-stimulatory molecules, as well as functional MHC class I molecules, which stimulate antigen-specific CD8+ T cell clones in vitro. Importantly, exosomes produced by tumor peptide-loaded DCs prime specific cytotoxic T lymphocytes in viva and eradicate established tumors. In addition, the secretion of exosomes by DCs is upregulated by IFNg, IL-12 and IL-IO, but not by TNF alpha or LPS, which efficiently induce DC maturation. The potent antitumor immune response induced by exosomes supports their implementation for cancer immunotherapy. In addition, exosomes may represent a novel "liposome Iike" means of communication between cells of the immune system.