Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1

	Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1
	Xiao, G; Deng, AQ; Liu, HF; Ge, GX; Liu, XL
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2012
卷号	109 期号:38 页码:15419-15424
关键词	antitumor immunity T cell response transactivation
通讯作者	Liu, XL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,liux@sibs.ac.cn
英文摘要	T cells play a critical role in tumor immunosurveillance by eliminating newly transformed somatic cells. However, tumor cell variants can escape from immunological control after immunoediting, leading to tumor progression. Whether and how T cells respond to tumor growth remain unclear. Here, we found that tumor-infiltrating T cells exhibited persistently up-regulated expression of the activator protein 1 (AP-1) subunit c-Fos during tumor progression. The ectopic expression of c-Fos in T cells exacerbated tumor growth, whereas the T-cell-specific deletion of c-Fos reduced tumor malignancy. This unexpected immunosuppressive effect of c-Fos was mediated through the induced expression of immune inhibitory receptor programmed death 1 (PD-1) via the direct binding of c-Fos to the AP-1-binding site in the Pdcd1 (gene encoding PD-1) promoter. A knock-inmutation of this binding site abrogated PD-1 induction, augmented antitumor T-cell function and repressed tumor growth. Taken together, these findings indicate that T-cell c-Fos subsequently induces PD-1 expression in response to tumor progression and that disrupting such induction is essential for repression of tumor growth.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	C-FOS ; ADAPTIVE IMMUNITY ; PD-1 EXPRESSION ; CANCER ; TRANSCRIPTION ; RECEPTOR ; MICE ; AP-1 ; TOLERANCE ; SELECTION
收录类别	SCI
语种	英语
WOS记录号	WOS:000309211000071
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/694]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Xiao, G,Deng, AQ,Liu, HF,et al. Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2012,109(38):15419-15424.
APA	Xiao, G,Deng, AQ,Liu, HF,Ge, GX,&Liu, XL.(2012).Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,109(38),15419-15424.
MLA	Xiao, G,et al."Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109.38(2012):15419-15424.