首页 / 院系成果 / 成果详情页

Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate PoorOutcomein Hepatocellular Carcinoma 期刊论文

编号：

611423c0-aecf-45dd-9055-9dcf7b9b7bb2
作者：

Duan, Meng^[1,2];Goswami, Shyamal^[3];Shi, JieYi^[1,2];Wu, LinJie^[4];Wang, XiaoYing^[1,2];Ma, JiaQiang^[3];Zhang, Zhao^[1,2];Shi, Yang^[5];Ma, LiJie^[1,2];Zhang, Shu^[1,2];Xi, RuiBin^[4,6];Cao, Ya^[7];Zhou, Jian(周俭)^[1,2,8,9]Fan, Jia(樊嘉)^[1,2,8,9]Zhang, XiaoMing^[3];Gao, Qiang(高强)^[1,2,9]
语种：

英文
期刊：

CLINICAL CANCER RESEARCH ISSN：1078-0432 2019 年 25 卷 11 期 (3304 - 3316) ; JUN 1
收录：
摘要：

Purpose: Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC).
Experimental Design: The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and in vitro bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC.
Results: Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosaassociated organs. Tumor-derived MAIT cells displayed a typical CCR7(+) CD45RA(+) CD45RO(+) CD95(+) effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educatedMAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNg and IL17, andproducedminimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretionand cytolysis effector function likeNFKB1 and STAT5B and by upregulating genes like IL8, CXCL12, and HAVCR2 (TIM-3). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively.
Conclusions: HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction.
推荐引用方式
GB/T 7714：

Duan Meng,Goswami Shyamal,Shi Jie-Yi, et al. Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate PoorOutcomein Hepatocellular Carcinoma [J].CLINICAL CANCER RESEARCH,2019,25(11):3304-3316.
APA：

Duan Meng,Goswami Shyamal,Shi Jie-Yi,Wu Lin-Jie,&Gao Qiang.(2019).Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate PoorOutcomein Hepatocellular Carcinoma .CLINICAL CANCER RESEARCH,25(11):3304-3316.
MLA：

Duan Meng, et al. "Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate PoorOutcomein Hepatocellular Carcinoma" .CLINICAL CANCER RESEARCH 25,11(2019):3304-3316.

浏览次数：9  下载次数：0

分享到：

浏览次数：9

下载次数：0

打印次数：0