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
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Miao-Fen Chen1,2, Feng-Che Kuan2,3, Tzu-Chen Yen4,5 , Ming-Shian Lu6, Paul-Yang Lin7, Yi-Hsiu Chung5, Wen-Cheng Chen1,2 and Kuan-Der Lee2,3
1 Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan
2 Chang Gung University, College of Medicine, Taiwan
3 Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan
4 Nuclear Medicine Department, Chang Gung Memorial Hospital at Linko, Taiwan
5 Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, at Linko, Taiwan
6 Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Chiayi, Taiwan
7 Pathology, Chang Gung Memorial Hospital at Chiayi, Taiwan
Miao-Fen Chen , email:
Keywords: IL-6; esophageal SCC; MDSC
Received: July 07, 2014 Accepted: August 18, 2014 Published: August 19, 2014
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.
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