Role of exosomes in immune regulation

Abstract

Exosomes are small vesicles originating from late endosomes, 30–100 nm in diameter with typical cup-shape morphology. They are reported to bear high levels of a narrow spectrum of molecules involved in immune response and signal transduction. Apart from removing obsolete membrane proteins, some surprising biological functions of exosomes were unveiled recently and their applications in immunotherapy of tumors are currently intensively investigated. Dendritic cell- (DC) and tumor-derived exosomes have considerable anti-tumor effects in experimental studies and several clinical trials. Despite their potential applications in eliciting a “positive” immune response, exosomes might induce some “unwanted” immune responses, such as immune tolerance and immune evasion. Therefore further investigations about the physiological functions of exosomes and the optimal way of exosome application in tumor immunotherapy are necessary. This review presents recent developments in the field of exosome research and focuses on its applications to tumor immunotherapy.

Caspase-3-dependent export of TCTP: a novel pathway for antiapoptotic intercellular communication

“…15,[21][22][23] Their precursors are intracellular vesicles packaged into MVB, which fuse with the plasma membrane, releasing exosomal vesicles into the extracellular milieu. 15,[21][22][23] Exosome-like nanovesicles are somewhat smaller (20-50 nm), of irregular shape and probably stem also from endosomal compartments. 15 Apoptotic blebs are bigger (50-500 nm), of heterogenous shapes and result from budding of the cell membrane.…”

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

“…Exosomes produced from mature dendritic cells express high levels of both MHCI and MHCII, as well as costimulatory and adhesion ligands. In contrast, exosomes from immature DCs show a different protein profile including NFGE8 (a phagocytosis-inducing factor), FasL, and TRAIL (an apoptosis-inducing ligand) (Li et al, 2006). Recent data suggest that exosomes from tumor cells often express immunosuppressive ligands, such as NKG2D, whose expression allows the evasion of tumor cells from T cell and NK cell killing (Clayton et al, 2008).…”

“…While that result can be interpreted that DCs provide T cells with the bystander costimulatory ligands and cytokines necessary to promote T cell activation, it is also possible that cognate peptides in exosomes are transferred to MHCs intrinsically expressed by DCs after uptake. Indeed, one study has shown that CD4 + T cells are activated only when both exosomes and DCs express MHCII and fail to be activated when DCs lacking MHCII are used (Li et al, 2006).…”

P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways

“…When released from leukocytes that have internalized and processed microbial or other foreign proteins, exosomes will contain MHCII loaded with antigenic peptide (pMHCII exosomes) [115]. A growing literature indicates that these released pMHCII exosomes can activate remote T lymphocytes either by direct antigen presentation from the pMHCII displayed on the exosome surface, or an indirect pathway wherein the pMHCII exosomes are taken up by remote naive dendritic cells for DC-mediated antigen presentation [116][117][118]. In addition to this model of "remote" antigen presentation, released exosomes may be used for other novel types of intercellular communication including the cell-to-cell transfer of: (1) intact mRNAs and microRNAs [119]; and (2) the direct transfer of oncogenic growth factor receptors from tumor cells to remote non-transformed cells [120].…”