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Immunotherapeutic Potential of Extracellular Vesicles

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Review

Immunotherapeutic Potential of Extracellular Vesicles

Bin Zhang et al. Front Immunol.

Abstract

Extracellular vesicle or EV is a term that encompasses all classes of secreted lipid membrane vesicles. Despite being scientific novelties, EVs are gaining importance as a mediator of important physiological and pathological intercellular activities possibly through the transfer of their cargo of protein and RNA between cells. In particular, exosomes, the currently best characterized EVs have been notable for their in vitro and in vivo immunomodulatory activities. Exosomes are nanometer-sized endosome-derived vesicles secreted by many cell types and their immunomodulatory potential is independent of their cell source. Besides immune cells such as dendritic cells, macrophages, and T cells, cancer and stem cells also secrete immunologically active exosomes that could influence both physiological and pathological processes. The immunological activities of exosomes affect both innate and adaptive immunity and include antigen presentation, T cell activation, T cell polarization to regulatory T cells, immune suppression, and anti-inflammation. As such, exosomes carry much immunotherapeutic potential as a therapeutic agent and a therapeutic target.

Keywords: adaptive immunity; exosomes; extracellular vesicles; immunomodulation; immunotherapy; innate immunity.

Figures

Figure 1
Figure 1
Exosome biogenesis and secretion. Exosomes are released by cells when intracellular organelles called multivesicular bodies (MVBs) fuse with the plasma membrane. MVBs are formed by invaginations of late endosomes, which contained molecules from the Golgi (e.g., MHC class II molecules) or the cell surface (e.g., growth factor receptors). Consequently, exosomes contain cytosolic materials and are enriched in endosome-associated protein markers such as the the Rab proteins, ALIX, TSG101, and MHC class II molecules or endocytic proteins, such as transferrin receptors and clathrins. This figure was modified from Lai et al. (169).
Figure 2
Figure 2
Exosomes from immune cells are shown. This figure summarizes the different known activities of exosomes from immune cells. (A) B cell secretes exosomes carrying MHC class II–peptide complexes as a mode of antigen presentation to primed CD4+ T cell. (B) DC-derived exosomes carry MHC class I or II-peptide complexes that can be either directly recognized by pre-activated CD4+ or CD8+ T cells or captured and presented by DCs to activate naïve T cells. (C) Macrophages infected with pathogens secrete exosomes with pathogen antigens. These exosomes induce maturation of DCs and promote secretion of pro-inflammatory cytokines.
Figure 3
Figure 3
Exosomes from tumor cells are shown. Tumor cell-derived exosomes can be either immune suppressive or activating. These exosomes exert some of their immune suppressive activities on T cells through FasL, galectin-9, TGFβ, or NKG2D ligand carried by the exosomes. Others inhibit differentiation of DCs or MDSCs through unknown mechanisms. However, tumor cell-derived exosomes also carry tumor antigens that could elicit an anti-tumor response.
Figure 4
Figure 4
Exosomes from normal tissues are shown. Normal tissue-derived exosomes exert multiple immune-modulatory activities to support normal physiological processes such as embryo implantation, fertilization, pregnancy, and oral tolerance.

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