Identification and functional analysis of heterogeneous FOXP3^+ Treg cell subpopulations in human pancreatic ductal adenocarcinoma

作     者：Gang Yi Shiwei Guo Wenyu Liu Huan Wang Rendong Liu Andy Tsun Gang Jin Bin Li 

作者机构：Shanghai Key Laboratory of Bio-energy Crops School of Life Science Shanghai University Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine CAS Center for Excellence in Molecular Cell Science Unit of Molecular Immunology Institute Pasteur of Shanghai Shanghai Institutes for Biological Sciences University of Chinese Academy of Sciences Medical School Chinese Academy of Sciences Department of General Surgery Changhai Hospital Second Military Medical University 

出 版 物：《Science Bulletin》 (科学通报（英文版）)

年 卷 期：2018年第63卷第15期

页      面：972-981页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by National Basic Research Program of China(2014CB541803 and 2014CB541903) the National Science Foundation of China(31525008,81330072,31670911,31370863 SMCST 14JC1406100) Shanghai Academic Research Leader(16XD1403800) 

主　　题：房间 胰腺 腺癌 cytokines 鉴定 异构 太阳神 IL-2 

摘      要：CD4^+CD25^+regulatory T(Treg) cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes(TDLNs) has been reported to correlate with both poor and favorable prognosis in various cancers, which suggests that Tregs may have multiple effects on antitumor immunity. However, the heterogeneity of tumor^-and TDLN^-infiltrating Treg cells remains unclear. Here we provide heterogeneity analysis of tumor infiltrating human CD4^+Treg cells and their matched adjacent tissues and TDLNs. We defined three different subpopulations of tumor^-and TDLN^-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma(PDAC) and confirmed their functional heterogeneity. Helios^+CCR8^+Treg cells with potent suppressor function and limited IL^-2 and IFN^-c secretion were identified in tumors and TDLNs. On the contrary, Helios^-CCR8^-Treg cells have impaired suppressive activity, and elevated expression of pro^-inflammatory cytokines. More advanced grades of PDAC have predominantly Helios^+CCR8^+Treg cells and few Helios^-CCR8^-Treg cells both in tumors and TDLNs that suggests poor prognosis. These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.