Abstract
Extracellular vesicles (EVs) are a heterogenous group of membrane-surrounded structures. Besides serving as a harbor for the unwanted material exocytosed by cells, EVs play a critical role in conveying intact protein, genetic, and lipid contents that are important for intercellular communication. EVs, broadly comprised of microvesicles and exosomes, are released to the extracellular environment from nearly all cells either via shedding from the plasma membrane or by originating from the endosomal system. Exosomes are 40–150 nm, endosome-derived small EVs (sEVs) that are released by cells into the extracellular environment. This review focuses on the biological properties of immune cell-derived sEVs, including composition and cellular targeting and mechanisms by which these immune cell-derived sEVs influence tumor immunity either by suppressing or promoting tumor growth, are discussed. The final section of this review discusses how the biological properties of immune cell-derived sEVs can be manipulated to improve their immunogenicity.
Highlights
In the first marathon, run solo by Philippides, both the messenger and the message were targeted
The final part of this review describes how the biological properties of these immune cell-derived Extracellular vesicles (EVs) can be engineered to amplify their immunogenicity as novel anti-cancer immunotherapeutic agents
SEVs can be manipulated to promote immunogenicity against cancer, and such bioengineered small EVs (sEVs) can function as efficient cancer vaccines
Summary
Run solo by Philippides, both the messenger and the message were targeted ( sadly the messenger died having delivered the message). SEVs in the extracellular milieu can transfer their contents to a target cell and influence its function and phenotype This transfer process involves a sequence of events that include docking of sEVs at the plasma membrane, surface receptor activation/signaling by the target cell, and endocytosis of the vesicle or its fusion with target cells. DC-derived sEVs loaded with tumor lysate enriched with molecular chaperone family of proteins such as calreticulin and heat shock protein 70 and 90 are reported to present a superior source of tumor antigens and immune responses in vivo than that offered with sEVs loaded with lysates obtained from freezing/thawing of tumor cells [77]. The antigenic drift and a highly immune suppressive tumor microenvironment present in the non-T cell inflamed tumors could be important contributing factors for the therapeutic failure
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