Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-gamma-induced immunologic dormancy of tumor-repopulating cells

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-gamma-induced immunologic dormancy of tumor-repopulating cells
	Huang, Bo; Liang, Xiaoyu; Liu, Yuying; Ji, Tiantian; Zhang, Huafeng; Dong, Wenqian; Jin, Xun; Chen, Degao; Li, Yanchun; Zhang, Songyan
刊名	NATURE COMMUNICATIONS
	2017-03-28
卷号	8 期号:0 页码:-
英文摘要	Interactions with the immune system may lead tumorigenic cells into dormancy. However, the underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-gamma induces tumour-repopulating cells (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-gamma signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as in TRCs, IFN-gamma results in IDO1/AhR-dependent p27 induction that prevents STAT1 signalling, thus suppressing the process of cell death and activating the dormancy program. Blocking the IDO/AhR metabolic circuitry not only abrogates IFN-gamma-induced dormancy but also results in enhanced repression of tumour growth by IFN-gamma-induced apoptosis of TRCs both in vitro and in vivo. These data present a previously unrecognized mechanism of inducing TRC dormancy by IFN-gamma, suggesting a potential effective cancer immunotherapeutic modality through the combination of IFN-gamma and IDO/AhR inhibitors.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/39261]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Huang, Bo,Liang, Xiaoyu,Liu, Yuying,et al. Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-gamma-induced immunologic dormancy of tumor-repopulating cells[J]. NATURE COMMUNICATIONS,2017,8(0):-.
APA	Huang, Bo.,Liang, Xiaoyu.,Liu, Yuying.,Ji, Tiantian.,Zhang, Huafeng.,...&Lv, Jiadi.(2017).Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-gamma-induced immunologic dormancy of tumor-repopulating cells.NATURE COMMUNICATIONS,8(0),-.
MLA	Huang, Bo,et al."Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-gamma-induced immunologic dormancy of tumor-repopulating cells".NATURE COMMUNICATIONS 8.0(2017):-.