Abstract
Exosomes are virus-sized nanoparticles (30–130 nm) formed intracellularly as intravesicular bodies/intralumenal vesicles within maturing endosomes (“multivesicular bodies”, MVBs). If MVBs fuse with the cell’s plasma membrane, the interior vesicles may be released extracellularly, and are termed “exosomes”. The protein cargo of exosomes consists of cytosolic, membrane, and extracellular proteins, along with membrane-derived lipids, and an extraordinary variety of nucleic acids. As such, exosomes reflect the status and identity of the parent cell, and are considered as tiny cellular surrogates. Because of this closely entwined relationship between exosome content and the source/status of the parental cell, conceivably exosomes could be used as vaccines against various pathologies, as they contain antigens associated with a given disease, e.g., cancer. Tumor-derived exosomes (TEX) have been shown to be potent anticancer vaccines in animal models, driving antigen-specific T and B cell responses, but much recent literature concerning TEX strongly places the vesicles as powerfully immunosuppressive. This dichotomy suggests that the context in which the immune system encounters TEX is critical in determining immune stimulation versus immunosuppression. Here, we review literature on both sides of this immune coin, and suggest that it may be time to revisit the concept of TEX as anticancer vaccines in clinical settings.
Highlights
Extracellular vesicles such as exosomes and microvesicles are reasonably considered to be important players in both the normal and pathological functions of cells, organs, and organisms [1]
Intradermal/subcutaneous delivery seems to lead to uptake by CD11c+ dendritic cells (DCs) that eventually migrate to the draining lymph node [159]; another model found that CD8+ DCs were exosome recipients via the integrin LFA-1 (CD11a/CD18) [160]
Tumor-derived exosomes (TEX) natively immunosuppress and facilitate tumor progression, they are important sources of tumor antigens, with potential clinical application in immune stimulation. This is the dichotomy of TEXual responses in cancer immunity
Summary
Extracellular vesicles such as exosomes and microvesicles are reasonably considered to be important players in both the normal and pathological functions of cells, organs, and organisms [1]. Their roles in many biologic processes [2] are increasingly recognized, if not understood, including in immune function/dysfunction in relation to cancer [3,4,5]. We will review some of the immune properties of exosomes/microvesicles in the context of cancer biology, where the vesicles may play dual roles in terms of immune stimulators (potentially having vaccine characteristics) and immune suppressors. We will argue that this dichotomy is likely due to the context in which the immune system sees the vesicles, and those circumstances may be deciding factors in the direction taken by the immune response
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