CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion

Abstract Extracellular vesicles are involved in the occurrence, progression and metastasis of glioblastoma (GBM). GBM can secrete a variety of tumour-derived extracellular vesicles (TDEVs) with high immunosuppressive activity that remotely suppress the systemic immune system, and therapy targeting T...

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Autores principales:	Ming Wang, Jiaoying Jia, Yan Cui, Yong Peng, Yugang Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/938cd1214546425da9692985f0ad213e
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spelling	oai:doaj.org-article:938cd1214546425da9692985f0ad213e2021-11-14T12:06:36ZCD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion10.1038/s41419-021-04359-32041-4889https://doaj.org/article/938cd1214546425da9692985f0ad213e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04359-3https://doaj.org/toc/2041-4889Abstract Extracellular vesicles are involved in the occurrence, progression and metastasis of glioblastoma (GBM). GBM can secrete a variety of tumour-derived extracellular vesicles (TDEVs) with high immunosuppressive activity that remotely suppress the systemic immune system, and therapy targeting TDEVs has potential efficacy. In this study, we detected a higher concentration of CD73+ TDEVs enriched in exosomes in central and peripheral body fluids of GBM patients than in those of patients with other brain tumours (low-grade glioma or brain metastases from melanoma or non-small-cell lung cancer). High CD73 expression was detected on the surface of T cells, and this CD73 was derived from TDEVs secreted by GBM cells. In vitro, we observed that CD73+ TDEVs released by GBM cell lines could be taken up by T cells. Moreover, excess adenosine was produced by AMP degradation around T cells and by adenosine receptor 2A (A2AR)-dependent inhibition of aerobic glycolysis and energy-related metabolic substrate production, thereby inhibiting the cell cycle entry and clonal proliferation of T cells. In vivo, defects in exosomal synthesis and CD73 expression significantly inhibited tumour growth in GBM tumour-bearing mice and restored the clonal proliferation of T cells in the central and peripheral regions. These data indicate that CD73+ TDEVs can be used as a potential target for GBM immunotherapy.Ming WangJiaoying JiaYan CuiYong PengYugang JiangNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Ming Wang Jiaoying Jia Yan Cui Yong Peng Yugang Jiang CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion
description	Abstract Extracellular vesicles are involved in the occurrence, progression and metastasis of glioblastoma (GBM). GBM can secrete a variety of tumour-derived extracellular vesicles (TDEVs) with high immunosuppressive activity that remotely suppress the systemic immune system, and therapy targeting TDEVs has potential efficacy. In this study, we detected a higher concentration of CD73+ TDEVs enriched in exosomes in central and peripheral body fluids of GBM patients than in those of patients with other brain tumours (low-grade glioma or brain metastases from melanoma or non-small-cell lung cancer). High CD73 expression was detected on the surface of T cells, and this CD73 was derived from TDEVs secreted by GBM cells. In vitro, we observed that CD73+ TDEVs released by GBM cell lines could be taken up by T cells. Moreover, excess adenosine was produced by AMP degradation around T cells and by adenosine receptor 2A (A2AR)-dependent inhibition of aerobic glycolysis and energy-related metabolic substrate production, thereby inhibiting the cell cycle entry and clonal proliferation of T cells. In vivo, defects in exosomal synthesis and CD73 expression significantly inhibited tumour growth in GBM tumour-bearing mice and restored the clonal proliferation of T cells in the central and peripheral regions. These data indicate that CD73+ TDEVs can be used as a potential target for GBM immunotherapy.
format	article
author	Ming Wang Jiaoying Jia Yan Cui Yong Peng Yugang Jiang
author_facet	Ming Wang Jiaoying Jia Yan Cui Yong Peng Yugang Jiang
author_sort	Ming Wang
title	CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion
title_short	CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion
title_full	CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion
title_fullStr	CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion
title_full_unstemmed	CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion
title_sort	cd73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting t-cell clonal expansion
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/938cd1214546425da9692985f0ad213e
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_version_	1718429476472225792

CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion

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