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Glucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression by inducing IL-9-producing helper T cells

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dc.contributor.authorKim I.-K.-
dc.contributor.authorKim B.-S.-
dc.contributor.authorKoh C.-H.-
dc.contributor.authorSeok J.-W.-
dc.contributor.authorPark J.-S.-
dc.contributor.authorShin K.-S.-
dc.contributor.authorBae E.-A.-
dc.contributor.authorLee G.-E.-
dc.contributor.authorJeon H.-
dc.contributor.authorCho J.-
dc.contributor.authorJung Y.-
dc.contributor.authorDaehee Han-
dc.contributor.authorKwon B.S.-
dc.contributor.authorLee H.-Y.-
dc.contributor.authorChung Y.-
dc.contributor.authorKang C.-Y.-
dc.date.available2016-01-07T09:10:47Z-
dc.date.created2015-09-21-
dc.date.issued2015-09-
dc.identifier.issn1078-8956-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/1877-
dc.description.abstractT cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra-/-) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4+ T-helper (T<inf>H</inf>9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-κB-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T<inf>H</inf>9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies. © 2015 Nature America, Inc. All rights reserved-
dc.description.uri1-
dc.language영어-
dc.publisherNATURE PUBLISHING GROUP-
dc.titleGlucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression by inducing IL-9-producing helper T cells-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000360961300013-
dc.identifier.scopusid2-s2.0-84941022982-
dc.identifier.rimsid21061ko
dc.date.tcdate2018-10-01-
dc.contributor.affiliatedAuthorDaehee Han-
dc.identifier.doi10.1038/nm.3922-
dc.identifier.bibliographicCitationNATURE MEDICINE, v.21, no.9, pp.1010 - 1017-
dc.citation.titleNATURE MEDICINE-
dc.citation.volume21-
dc.citation.number9-
dc.citation.startPage1010-
dc.citation.endPage1017-
dc.date.scptcdate2018-10-01-
dc.description.wostc39-
dc.description.scptc45-
dc.description.journalClass1-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
14. (2015-Nature Medicine) Glucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression~.pdfDownload

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