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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Nitroquinoline-1-oxide
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Animals
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Arginase / metabolism
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CD11b Antigen / immunology
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CD11b Antigen / metabolism*
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Carcinoma, Squamous Cell / chemically induced
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Carcinoma, Squamous Cell / immunology
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Carcinoma, Squamous Cell / therapy
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Case-Control Studies
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Cells, Cultured
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Disease Progression
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Esophageal Neoplasms / chemically induced
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Esophageal Neoplasms / immunology
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Esophageal Neoplasms / metabolism*
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Esophageal Neoplasms / pathology
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Esophageal Neoplasms / therapy
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Esophageal Squamous Cell Carcinoma
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HLA-DR Antigens / immunology
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HLA-DR Antigens / metabolism*
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Humans
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Interleukin-6 / deficiency
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Interleukin-6 / metabolism*
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Lipopolysaccharide Receptors / immunology
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Lipopolysaccharide Receptors / metabolism*
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Male
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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Cells / immunology
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Myeloid Cells / metabolism*
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Myeloid Cells / pathology
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Neoplasm Staging
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Phosphorylation
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Quinolones
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Reactive Oxygen Species / metabolism
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STAT3 Transcription Factor / metabolism
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Signal Transduction
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Time Factors
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Treatment Outcome
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Tumor Burden
Substances
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4-nitroquinolone-1-oxide
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CD11b Antigen
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HLA-DR Antigens
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IL6 protein, human
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ITGAM protein, human
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Interleukin-6
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Lipopolysaccharide Receptors
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Quinolones
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Reactive Oxygen Species
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STAT3 Transcription Factor
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Stat3 protein, mouse
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interleukin-6, mouse
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4-Nitroquinoline-1-oxide
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Arg1 protein, mouse
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Arginase