Dendritic cell-derived exosomes as cell-free peptide-based vaccines

Dendritic cells (DC) are professional antigen-presenting cells and the only ones capable of inducing primary cytotoxic immune responses both in vivo and in vitro. DCs secrete a 60-100 nm membrane vesicle population of endocytic origin, called exosomes. The lipid and protein composition of DC-derived exosomes (DEX) is now well characterized. Besides MHC and costimulatory molecules, DEX bear several adhesion proteins, which are probably involved in their specific targeting. DEX also accumulate several cytosolic factors, most likely involved in exosome's biogenesis in late endosomes. In 1998, we reported that DEX are immunogenic in mice and lead to tumor rejection. These findings have renewed the interest in DEX. The current challenge consists of understanding the mechanisms and the physiological relevance of DEX, which could contribute to the design of the optimal DEX-based vaccination. In this review, we focus on the biological features of DEX and their immunostimulatory functions in mice and humans, and we discuss their potential clinical implementation in the immunotherapy of cancer.