Exosomes: composition, biogenesis and function

Exosomes are saucer-shaped vesicles of 30–100 nm in diameter, which are delimited by a lipid bi-layer and which float at a density of 1.13–1.19 g ml−1 in sucrose gradients. These vesicles are secreted by various cells in culture. Analysis of the protein composition of exosomes that are secreted by various cells reveals the presence of some common proteins, which define exosomes as a bona fide secreted subcellular compartment, as well as the presence of some cell-type-specific proteins, which could mediate the different functions of exosomes that are produced by different cell types. All of the proteins that have been identified in exosomes are localized in the cell cytosol or endosomal compartments, never in the endoplasmic reticulum, Golgi apparatus, mitochondria or nucleus. Exosomes also contain some plasma-membrane proteins, which have been described also in endosomal compartments. These observations are consistent with the proposed origin of exosomes as internal vesicles of late multivesicular compartments. Formation of the internal vesicles of multivesicular bodies by inward budding from the limiting membrane involves a budding event of inverse membrane orientation compared with the classical intracellular budding events that take place in a cell. All inverse budding events seem to be correlated with an inversion of the transmembrane partition of the lipid phosphatidylserine. Membrane exchanges between cells have been described during the interactions of T cells and antigen-presenting cells (from the T cell to the antigen-presenting cell, or reciprocally, depending on the analyses), or between dendritic cells. It is not clear whether such exchanges involve exosomes. The biological functions of exosomes remain unclear. The original role of exosomes was most probably to eliminate undegraded endosomal or lysosomal proteins and membranes. Recent results indicate, however, that in different cell types, exosomes might have other functions, such as the stimulation or inactivation of T cells, or the transfer of antigens to dendritic cells. Regardless of their putative physiological functions, exosomes have been used successfully in preclinical mouse and human tumour immunotherapy assays. A Phase I clinical trial in melanoma patients is ongoing.