Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a

Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased num...

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Autores principales:	Yuta Nakazawa, Nanako Nishiyama, Hitoshi Koizumi, Kazumasa Kanemaru, Chigusa Nakahashi-Oda, Akira Shibuya
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	tumor-infiltrating regulatory T cells tumor-derived extracellular vesicles immunoreceptor dendritic cells IFN-b CD300a Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/91964b93598b4425b65c3c2ccca83d64
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spelling	oai:doaj.org-article:91964b93598b4425b65c3c2ccca83d642021-11-09T13:06:00ZTumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a10.7554/eLife.619992050-084Xe61999https://doaj.org/article/91964b93598b4425b65c3c2ccca83d642021-11-01T00:00:00Zhttps://elifesciences.org/articles/61999https://doaj.org/toc/2050-084XAlthough tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice. Coculture of DCs with tumor-derived EV (TEV) induced the internalization of CD300a and the incorporation of EVs into endosomes, in which CD300a inhibited TEV-mediated TLR3–TRIF signaling for activation of the IFN-β-Treg cells axis. We also show that higher expression of CD300A was associated with decreased tumor-infiltrating Treg cells and longer survival time in patients with melanoma. Our findings reveal the role of TEV and CD300a on DCs in Treg cell activation in the tumor microenvironment.Yuta NakazawaNanako NishiyamaHitoshi KoizumiKazumasa KanemaruChigusa Nakahashi-OdaAkira ShibuyaeLife Sciences Publications Ltdarticletumor-infiltrating regulatory T cellstumor-derived extracellular vesiclesimmunoreceptordendritic cellsIFN-bCD300aMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumor-infiltrating regulatory T cells tumor-derived extracellular vesicles immunoreceptor dendritic cells IFN-b CD300a Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	tumor-infiltrating regulatory T cells tumor-derived extracellular vesicles immunoreceptor dendritic cells IFN-b CD300a Medicine R Science Q Biology (General) QH301-705.5 Yuta Nakazawa Nanako Nishiyama Hitoshi Koizumi Kazumasa Kanemaru Chigusa Nakahashi-Oda Akira Shibuya Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
description	Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice. Coculture of DCs with tumor-derived EV (TEV) induced the internalization of CD300a and the incorporation of EVs into endosomes, in which CD300a inhibited TEV-mediated TLR3–TRIF signaling for activation of the IFN-β-Treg cells axis. We also show that higher expression of CD300A was associated with decreased tumor-infiltrating Treg cells and longer survival time in patients with melanoma. Our findings reveal the role of TEV and CD300a on DCs in Treg cell activation in the tumor microenvironment.
format	article
author	Yuta Nakazawa Nanako Nishiyama Hitoshi Koizumi Kazumasa Kanemaru Chigusa Nakahashi-Oda Akira Shibuya
author_facet	Yuta Nakazawa Nanako Nishiyama Hitoshi Koizumi Kazumasa Kanemaru Chigusa Nakahashi-Oda Akira Shibuya
author_sort	Yuta Nakazawa
title	Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
title_short	Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
title_full	Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
title_fullStr	Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
title_full_unstemmed	Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
title_sort	tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory t cells via the inhibitory immunoreceptor cd300a
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/91964b93598b4425b65c3c2ccca83d64
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Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a

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