IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector CD8(+) T cells in vivo

Shen, Weidong; Wang, Xiangdong; Xiang, Huihui; Shichi, Shunsuke; Nakamoto, Hiroki; Kimura, Saori; Sugiyama, Ko; Taketomi, Akinobu; Kitamura, Hidemitsu

IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector CD8(+) T cells in vivo

Shen, Weidong; Wang, Xiangdong; Xiang, Huihui et al.

Cancer science, 2023, 114(5), 1816-1829

Permalink : https://hdl.handle.net/2115/89264

このアイテムのアクセス数:895件（2026-01-19 14:58 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/89264
タイトル	IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector CD8(+) T cells in vivo
著者	Shen, Weidong ; Wang, Xiangdong ; Xiang, Huihui ; Shichi, Shunsuke ; Nakamoto, Hiroki ; Kimura, Saori ; Sugiyama, Ko ; Taketomi, Akinobu ; Kitamura, Hidemitsu
著者名 Shen, Weidong
著者名 Wang, Xiangdong
著者名 Xiang, Huihui
著者名 Shichi, Shunsuke
著者名 Nakamoto, Hiroki
著者名 Kimura, Saori
著者名 Sugiyama, Ko
著者名 Taketomi, Akinobu
e-Rad_Researcher 40360531 著者名 Kitamura, Hidemitsu
言語	英語
キーワード	effector CD8(+) T cells
	hepatocellular carcinoma
	IFN-gamma
	NK2R
	STAT1
発行日	2023-05
出版者	John Wiley & Sons
収録物名	Cancer science
巻(号)	114(5)
ページ	1816-1829
抄録	The induction of antitumor effector T cells in the tumor microenvironment is a crucial event for cancer immunotherapy. Neurokinin receptor 2 (NK2R), a G protein-coupled receptor for neurokinin A (NKA), regulates diverse physiological functions. However, the precise role of NKA-NK2R signaling in antitumor immunity is unclear. Here, we found that an IFN-gamma-STAT1 cascade augmented NK2R expression in CD8(+) T cells, and NK2R-mediated NKA signaling was involved in inducing antitumor effector T cells in vivo. The administration of a synthetic analog of double-stranded RNA, polyinosinic-polycytidylic acid (poly I:C), into a liver cancer mouse model induced type I and type II IFNs and significantly suppressed the tumorigenesis of Hepa1-6 liver cancer cells in a STAT1-dependent manner. The reduction in tumor growth was diminished by the depletion of CD8(+) T cells. IFN-gamma stimulation significantly induced NK2R and tachykinin precursor 1 (encodes NKA) gene expression in CD8(+) T cells. NKA stimulation combined with anti-CD3 monoclonal antibody (mAb) treatment significantly augmented IFN-gamma and granzyme B production by CD8(+) T cells compared with the anti-CD3 mAb alone in vitro. ERK1/2 phosphorylation and I kappa B alpha degradation in activated CD8(+) T cells were suppressed under NK2R deficiency. Finally, we confirmed that tumor growth was significantly increased in NK2R-deficient mice compared with that in wild-type mice, and the antitumor effects of poly I:C were abolished by NK2R absence. These findings suggest that IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector T cells in the tumor microenvironment, which contributes to the suppression of cancer cell tumorigenesis in vivo. In this study, we revealed that IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector CD8(+) T cells in the tumor microenvironment, which contributes to suppressing the tumorigenesis of liver cancer cells in vivo.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial 4.0 International
PISSN	1347-9032
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1111/cas.15738