Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma

Osteosarcoma (OS) is a malignant tumor commonly observed in adolescents, who experience relapse and metastasis (30% of the total cases). Its progression is attributed to immune escape mediated by immune checkpoints. However, the intercellular connection between tumor cells and T cells remain unclear...

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Autores principales:	Lei Zhang, Lili Xue, Yanjuan Wu, Qilong Wu, Hongwei Ren, Xiang Song
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	exosomes pd-l1 osteosarcoma t cells Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/166c80bbcc0a404e9ce206067c95cf83
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spelling	oai:doaj.org-article:166c80bbcc0a404e9ce206067c95cf832021-11-04T15:51:54ZExosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma2165-59792165-598710.1080/21655979.2021.1996509https://doaj.org/article/166c80bbcc0a404e9ce206067c95cf832021-10-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1996509https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Osteosarcoma (OS) is a malignant tumor commonly observed in adolescents, who experience relapse and metastasis (30% of the total cases). Its progression is attributed to immune escape mediated by immune checkpoints. However, the intercellular connection between tumor cells and T cells remain unclear. This study was conducted to explore the effects of PD-L1-loaded exosomes on the tumor growth of OS. The exosomes were extracted from cells and tissues through ultracentrifugation. IFN-γ production was determined to evaluate the activity of Jurkat cells. The in vivo growth of OS cells was examined using a C3H xenograft model in mice, tumor volumes were monitored, and the proportion of CD3+ T cells in tumor tissues was detected. Results revealed that PD-L1 was significantly upregulated in the OS cell lines. MG63 and Saos-2 cells were the most abundant in PD-L1, so they were selected as investigation targets. PD-L1 was found to be also highly expressed in the exosomes isolated from MG63 and Saos-2 cells. The exosomes elicited significant inhibitory effects on IFN-γ secretion in Jurkat cells, which were abolished by the PD-L1 antibody or siRNAs. The in vivo growth of C3H cells was significantly facilitated by the overexpression of mPD-L1 or by the administration of mPD-L1-overloaded exosomes. The infiltration of CD3+ T cells was also decreased. The exosomes extracted from clinical PD-L1-positive OS tissues showed a promising inhibitory property against activated T cells. Therefore, PD-L1-loaded exosomes extracted from OS cells aggravated OS progression by suppressing T cell activities.Lei ZhangLili XueYanjuan WuQilong WuHongwei RenXiang SongTaylor & Francis Grouparticleexosomespd-l1osteosarcomat cellsBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	exosomes pd-l1 osteosarcoma t cells Biotechnology TP248.13-248.65
spellingShingle	exosomes pd-l1 osteosarcoma t cells Biotechnology TP248.13-248.65 Lei Zhang Lili Xue Yanjuan Wu Qilong Wu Hongwei Ren Xiang Song Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma
description	Osteosarcoma (OS) is a malignant tumor commonly observed in adolescents, who experience relapse and metastasis (30% of the total cases). Its progression is attributed to immune escape mediated by immune checkpoints. However, the intercellular connection between tumor cells and T cells remain unclear. This study was conducted to explore the effects of PD-L1-loaded exosomes on the tumor growth of OS. The exosomes were extracted from cells and tissues through ultracentrifugation. IFN-γ production was determined to evaluate the activity of Jurkat cells. The in vivo growth of OS cells was examined using a C3H xenograft model in mice, tumor volumes were monitored, and the proportion of CD3+ T cells in tumor tissues was detected. Results revealed that PD-L1 was significantly upregulated in the OS cell lines. MG63 and Saos-2 cells were the most abundant in PD-L1, so they were selected as investigation targets. PD-L1 was found to be also highly expressed in the exosomes isolated from MG63 and Saos-2 cells. The exosomes elicited significant inhibitory effects on IFN-γ secretion in Jurkat cells, which were abolished by the PD-L1 antibody or siRNAs. The in vivo growth of C3H cells was significantly facilitated by the overexpression of mPD-L1 or by the administration of mPD-L1-overloaded exosomes. The infiltration of CD3+ T cells was also decreased. The exosomes extracted from clinical PD-L1-positive OS tissues showed a promising inhibitory property against activated T cells. Therefore, PD-L1-loaded exosomes extracted from OS cells aggravated OS progression by suppressing T cell activities.
format	article
author	Lei Zhang Lili Xue Yanjuan Wu Qilong Wu Hongwei Ren Xiang Song
author_facet	Lei Zhang Lili Xue Yanjuan Wu Qilong Wu Hongwei Ren Xiang Song
author_sort	Lei Zhang
title	Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma
title_short	Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma
title_full	Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma
title_fullStr	Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma
title_full_unstemmed	Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma
title_sort	exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/166c80bbcc0a404e9ce206067c95cf83
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Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma

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