Circulating myeloid-derived suppressor cells in patients with pancreatic cancer  

作　　者：Xiao-Dong Xu Jun Hu Min Wang Feng Peng Rui Tian Xing-Jun Guo Yu Xie Ren-Yi Qin 

机构地区：[1]Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]Department of Colon Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy,Tianjin 300060, China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2016年第1期99-105,共7页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(81071775,81272659,81101621,81160311,81172064,81001068,81272425 and 81101870);National“Eleventh Five-Year”Scientific and Technological Support Projects(2006BAI02A13-402);Key Projects of Science Foundation of Hubei Province(2011CDA030);Research Fund of Young Scholars for the Doctoral Program of Higher Education of China(20110142120014)

摘　　要：BACKGROUND： Myeloid-derived suppressor cells （MDSCs） are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS： Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co- cultured with normal peripheral blood mononudear cells （PBMCs） to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor （GM-CSF） and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS： CD14＋/CD11b＋/HLA-DR MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se rum of patients with pancreatic cancer. CONCLUSIONS： MDSCs were tumor related： tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14＋/CD11b＋/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.BACKGROUND： Myeloid-derived suppressor cells （MDSCs） are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS： Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co- cultured with normal peripheral blood mononudear cells （PBMCs） to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor （GM-CSF） and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS： CD14＋/CD11b＋/HLA-DR MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se rum of patients with pancreatic cancer. CONCLUSIONS： MDSCs were tumor related： tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14＋/CD11b＋/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.

关 键 词：pancreatic cancer myeloid-derived suppressor cells granulocyte- macrophage colony-stimulating factor ARGINASE 

分 类 号：R735.9[医药卫生—肿瘤]