Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production

Clayton, Aled; Al-Taei, Saly; Webber, Jason; Mason, Malcolm D.; Tabi, Zsuzsanna

doi:10.4049/jimmunol.1003884

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Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production

Aled Clayton, Saly Al-Taei, Jason Webber

, Malcolm D. Mason, Zsuzsanna Tabi

The Journal of Immunology, Volume: 187, Issue: 2, Pages: 676 - 683

Swansea University Author: Jason Webber

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DOI (Published version): 10.4049/jimmunol.1003884

Abstract

Extracellular adenosine is elevated in cancer tissue, and it negatively regulates local immune responses. Adenosine production from extracellular ATP has attracted attention as a mechanism of regulatory T cell-mediated immune regulation. In this study, we examined whether small vesicles secreted by...

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Published in:	The Journal of Immunology
ISSN:	0022-1767 1550-6606
Published:	The American Association of Immunologists 2011
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa64726
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first_indexed	2023-10-11T15:49:19Z
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spelling	v2 64726 2023-10-11 Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production 25d1a26f9b8bb556bd9412080e40351d 0000-0003-4772-3014 Jason Webber Jason Webber true false 2023-10-11 BMS Extracellular adenosine is elevated in cancer tissue, and it negatively regulates local immune responses. Adenosine production from extracellular ATP has attracted attention as a mechanism of regulatory T cell-mediated immune regulation. In this study, we examined whether small vesicles secreted by cancer cells, called exosomes, contribute to extracellular adenosine production and hence modulate immune effector cells indirectly. We found exosomes from diverse cancer cell types exhibit potent ATP- and 5′AMP-phosphohydrolytic activity, partly attributed to exosomally expressed CD39 and CD73, respectively. Comparable levels of activity were seen with exosomes from pleural effusions of mesothelioma patients. In such fluids, exosomes accounted for 20% of the total ATP-hydrolytic activity. Exosomes can perform both hydrolytic steps sequentially to form adenosine from ATP. This exosome-generated adenosine can trigger a cAMP response in adenosine A2A receptor-positive but not A2A receptor-negative cells. Similarly, significantly elevated cAMP was also triggered in Jurkat cells by adding exosomes with ATP but not by adding exosomes or ATP alone. A proportion of healthy donor T cells constitutively express CD39 and/or CD73. Activation of T cells by CD3/CD28 cross-linking could be inhibited by exogenously added 5′AMP in a CD73-dependent manner. However, 5′AMP converted to adenosine by exosomes inhibits T cell activation independently of T cell CD73 expression. This T cell inhibition was mediated through the adenosine A2A receptor. In summary, the data highlight exosome enzymic activity in the production of extracellular adenosine, and this may play a contributory role in negative modulation of T cells in the tumor environment. Journal Article The Journal of Immunology 187 2 676 683 The American Association of Immunologists 0022-1767 1550-6606 15 7 2011 2011-07-15 10.4049/jimmunol.1003884 http://dx.doi.org/10.4049/jimmunol.1003884 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee 2023-11-28T10:43:04.9778642 2023-10-11T16:48:40.4694910 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Aled Clayton 1 Saly Al-Taei 2 Jason Webber 0000-0003-4772-3014 3 Malcolm D. Mason 4 Zsuzsanna Tabi 5
title	Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
spellingShingle	Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production Jason Webber
title_short	Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
title_full	Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
title_fullStr	Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
title_full_unstemmed	Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
title_sort	Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production
author_id_str_mv	25d1a26f9b8bb556bd9412080e40351d
author_id_fullname_str_mv	25d1a26f9b8bb556bd9412080e40351d_***_Jason Webber
author	Jason Webber
author2	Aled Clayton Saly Al-Taei Jason Webber Malcolm D. Mason Zsuzsanna Tabi
format	Journal article
container_title	The Journal of Immunology
container_volume	187
container_issue	2
container_start_page	676
publishDate	2011
institution	Swansea University
issn	0022-1767 1550-6606
doi_str_mv	10.4049/jimmunol.1003884
publisher	The American Association of Immunologists
college_str	Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
url	http://dx.doi.org/10.4049/jimmunol.1003884
document_store_str	0
active_str	0
description	Extracellular adenosine is elevated in cancer tissue, and it negatively regulates local immune responses. Adenosine production from extracellular ATP has attracted attention as a mechanism of regulatory T cell-mediated immune regulation. In this study, we examined whether small vesicles secreted by cancer cells, called exosomes, contribute to extracellular adenosine production and hence modulate immune effector cells indirectly. We found exosomes from diverse cancer cell types exhibit potent ATP- and 5′AMP-phosphohydrolytic activity, partly attributed to exosomally expressed CD39 and CD73, respectively. Comparable levels of activity were seen with exosomes from pleural effusions of mesothelioma patients. In such fluids, exosomes accounted for 20% of the total ATP-hydrolytic activity. Exosomes can perform both hydrolytic steps sequentially to form adenosine from ATP. This exosome-generated adenosine can trigger a cAMP response in adenosine A2A receptor-positive but not A2A receptor-negative cells. Similarly, significantly elevated cAMP was also triggered in Jurkat cells by adding exosomes with ATP but not by adding exosomes or ATP alone. A proportion of healthy donor T cells constitutively express CD39 and/or CD73. Activation of T cells by CD3/CD28 cross-linking could be inhibited by exogenously added 5′AMP in a CD73-dependent manner. However, 5′AMP converted to adenosine by exosomes inhibits T cell activation independently of T cell CD73 expression. This T cell inhibition was mediated through the adenosine A2A receptor. In summary, the data highlight exosome enzymic activity in the production of extracellular adenosine, and this may play a contributory role in negative modulation of T cells in the tumor environment.
published_date	2011-07-15T10:43:05Z
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score	11.037581

Cancer Exosomes Express CD39 and CD73, Which Suppress T Cells through Adenosine Production

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