TIPE2 is a novel direct target of STAT3 in MDSC and inhibition of its expression on MDSC enhanced T cell activation in tumor

	TIPE2 is a novel direct target of STAT3 in MDSC and inhibition of its expression on MDSC enhanced T cell activation in tumor
	Xiaochun Wan; Jinghui Wang; Dehong Yan
刊名	JOURNAL OF IMMUNOLOGY
	2017
文献子类	期刊论文
英文摘要	MDSCs represent an immature population of myeloid cells that inhibit both innate and adaptive immunity in most cancer patients and mice bearing various tumors through several inflammatory mediators. TIPE2, a member of tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) family, is a negative regulator of innate and adaptive immunity. In this study, we investigated the influence of tumor-derived factors on TIPE2 expression in MDSCs. We demonstrate that tumor-derived IL-6 induced TIPE2 up-regulation expression of MDSCs. This effect was dependent on phosphorylation signal transducer of activator of transcription 3 (STAT3) and blockade of STAT3 signaling also reversed the effect of tumor-derived IL-6 on TIPE2 expression in MDSCs. Chromatin immunoprecipitation and luciferase reporter assay revealed direct binding of STAT3 to a transcriptionally active STAT3-response element (SRE) in the TIPE2 proximal promoter. Inhibition of TIPE2 expression on MDSCs by shRNA technology enhanced T cell activation and abrogated the suppressive activity of MDSCs. More importantly, downregulation of TIPE2 level on MDSCs by stattic, a STAT3 inhibitor, significantly delayed tumor growth in tumor-bearing mice. Targeting of TIPE2 therapy may represent a novel approach for cancer immunotherapy.
URL标识	查看原文
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/12282]
专题	深圳先进技术研究院_医药所
作者单位	JOURNAL OF IMMUNOLOGY
推荐引用方式 GB/T 7714	Xiaochun Wan,Jinghui Wang,Dehong Yan. TIPE2 is a novel direct target of STAT3 in MDSC and inhibition of its expression on MDSC enhanced T cell activation in tumor[J]. JOURNAL OF IMMUNOLOGY,2017.
APA	Xiaochun Wan,Jinghui Wang,&Dehong Yan.(2017).TIPE2 is a novel direct target of STAT3 in MDSC and inhibition of its expression on MDSC enhanced T cell activation in tumor.JOURNAL OF IMMUNOLOGY.
MLA	Xiaochun Wan,et al."TIPE2 is a novel direct target of STAT3 in MDSC and inhibition of its expression on MDSC enhanced T cell activation in tumor".JOURNAL OF IMMUNOLOGY (2017).