title: IL-6-stimulated CD11b+ CD14+ HLA-DR- myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus.
abstract: The aim of this study was to assess the significance of myeloid-derived suppressor cells (MDSCs) and their association with IL-6 in esophageal squamous cell carcinoma (SCC). We examined the percentage of CD11b+CD14+HLA-DR- myeloid cells and the levels of IL-6 in the peripheral blood of 50 patients with esophageal SCC and 12 healthy controls. Moreover, we evaluated the relationship between MDSC recruitment, IL-6 levels, and tumor progression by adding 4-nitroquinoline 1-oxide (4-NQO) to the drinking water of mice to induce esophageal tumors. Here we demonstrated that circulating CD11b+CD14+HLA-DR- cells were significantly increased in esophageal SCC patients compared with healthy people, and this was associated with the clinical stage, treatment response and circulating IL-6 levels. In a 4-NQO-induced esophageal tumor animal model, MDSC recruitment was associated with invasive esophageal tumors and with increased IL-6 levels. IL-6 stimulated reactive oxygen species, arginase 1 and p-STAT3 in MDSCs. Blockade of IL-6 prevented induction of MDSCs and the incidence of 4-NQO- induced invasive tumors. In conclusion, the levels of MDSCs and IL-6 predicted the prognosis of patients with esophageal SCC. Moreover, we suggest inhibition of IL-6 as a potential strategy for the treatment of esophageal SCC.
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan. Chang Gung University, College of Medicine, Taiwan.
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.affiliation: Chang Gung University, College of Medicine, Taiwan. Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
authors.forename: Feng-Che
authors.initials: FC
authors.lastname: Kuan
authors.affiliation: Nuclear Medicine Department, Chang Gung Memorial Hospital at Linko, Taiwan. Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, at Linko, Taiwan.
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.affiliation: Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Chiayi, Taiwan.
authors.forename: Ming-Shian
authors.initials: MS
authors.lastname: Lu
authors.affiliation: Pathology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
authors.forename: Paul-Yang
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, at Linko, Taiwan.
authors.forename: Yi-Hsiu
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan. Chang Gung University, College of Medicine, Taiwan.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Chang Gung University, College of Medicine, Taiwan. Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D001119:Arginase / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D002478:Cells, Cultured; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D010766:Phosphorylation; D015363:Quinolones; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: C120195:4-nitroquinolone-1-oxide; D039481:CD11b Antigen; D006684:HLA-DR Antigens; C508600:IL6 protein, human; C509295:ITGAM protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D015363:Quinolones; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse; D015112:4-Nitroquinoline-1-oxide; C544448:Arg1 protein, mouse; D001119:Arginase