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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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Title
Glucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression by inducing IL-9-producing helper T cells
Author(s)
Kim I.-K.; Kim B.-S.; Koh C.-H.; Seok J.-W.; Park J.-S.; Shin K.-S.; Bae E.-A.; Lee G.-E.; Jeon H.; Cho J.; Jung Y.; Daehee Han; Kwon B.S.; Lee H.-Y.; Chung Y.; Kang C.-Y.
Publication Date
2015-09
Journal
NATURE MEDICINE, v.21, no.9, pp.1010 - 1017
Publisher
NATURE PUBLISHING GROUP
Abstract
T 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 (TH9) 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 TH9 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
URI
https://pr.ibs.re.kr/handle/8788114/1877
ISSN
1078-8956
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > 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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