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Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments

Exosomes are a subset of extracellular vesicles (EVs) that are released by cells and play a variety of physiological roles including regulation of the immune system. Exosomes are heterogeneous and present in vast numbers in tumor microenvironments. A large subset of these vesicles has been demonstra...

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Autores principales: Shenoy, Gautam N., Bhatta, Maulasri, Bankert, Richard B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619102/
https://www.ncbi.nlm.nih.gov/pubmed/34831378
http://dx.doi.org/10.3390/cells10113155
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author Shenoy, Gautam N.
Bhatta, Maulasri
Bankert, Richard B.
author_facet Shenoy, Gautam N.
Bhatta, Maulasri
Bankert, Richard B.
author_sort Shenoy, Gautam N.
collection PubMed
description Exosomes are a subset of extracellular vesicles (EVs) that are released by cells and play a variety of physiological roles including regulation of the immune system. Exosomes are heterogeneous and present in vast numbers in tumor microenvironments. A large subset of these vesicles has been demonstrated to be immunosuppressive. In this review, we focus on the suppression of T cell function by exosomes in human tumor microenvironments. We start with a brief introduction to exosomes, with emphasis on their biogenesis, isolation and characterization. Next, we discuss the immunosuppressive effect of exosomes on T cells, reviewing in vitro studies demonstrating the role of different proteins, nucleic acids and lipids known to be associated with exosome-mediated suppression of T cell function. Here, we also discuss initial proof-of-principle studies that established the potential for rescuing T cell function by blocking or targeting exosomes. In the final section, we review different in vivo models that were utilized to study as well as target exosome-mediated immunosuppression, highlighting the Xenomimetic mouse (X-mouse) model and the Omental Tumor Xenograft (OTX) model that were featured in a recent study to evaluate the efficacy of a novel phosphatidylserine-binding molecule for targeting immunosuppressive tumor-associated exosomes.
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spelling pubmed-86191022021-11-27 Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments Shenoy, Gautam N. Bhatta, Maulasri Bankert, Richard B. Cells Review Exosomes are a subset of extracellular vesicles (EVs) that are released by cells and play a variety of physiological roles including regulation of the immune system. Exosomes are heterogeneous and present in vast numbers in tumor microenvironments. A large subset of these vesicles has been demonstrated to be immunosuppressive. In this review, we focus on the suppression of T cell function by exosomes in human tumor microenvironments. We start with a brief introduction to exosomes, with emphasis on their biogenesis, isolation and characterization. Next, we discuss the immunosuppressive effect of exosomes on T cells, reviewing in vitro studies demonstrating the role of different proteins, nucleic acids and lipids known to be associated with exosome-mediated suppression of T cell function. Here, we also discuss initial proof-of-principle studies that established the potential for rescuing T cell function by blocking or targeting exosomes. In the final section, we review different in vivo models that were utilized to study as well as target exosome-mediated immunosuppression, highlighting the Xenomimetic mouse (X-mouse) model and the Omental Tumor Xenograft (OTX) model that were featured in a recent study to evaluate the efficacy of a novel phosphatidylserine-binding molecule for targeting immunosuppressive tumor-associated exosomes. MDPI 2021-11-13 /pmc/articles/PMC8619102/ /pubmed/34831378 http://dx.doi.org/10.3390/cells10113155 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Shenoy, Gautam N.
Bhatta, Maulasri
Bankert, Richard B.
Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments
title Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments
title_full Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments
title_fullStr Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments
title_full_unstemmed Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments
title_short Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments
title_sort tumor-associated exosomes: a potential therapeutic target for restoring anti-tumor t cell responses in human tumor microenvironments
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619102/
https://www.ncbi.nlm.nih.gov/pubmed/34831378
http://dx.doi.org/10.3390/cells10113155
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