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

Oncotarget. 2014 Sep 30;5(18):8716-28. doi: 10.18632/oncotarget.2368.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Nitroquinoline-1-oxide
  • Animals
  • Arginase / metabolism
  • CD11b Antigen / immunology
  • CD11b Antigen / metabolism*
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Case-Control Studies
  • Cells, Cultured
  • Disease Progression
  • Esophageal Neoplasms / chemically induced
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy
  • Esophageal Squamous Cell Carcinoma
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism*
  • Humans
  • Interleukin-6 / deficiency
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism*
  • Myeloid Cells / pathology
  • Neoplasm Staging
  • Phosphorylation
  • Quinolones
  • Reactive Oxygen Species / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Time Factors
  • Treatment Outcome
  • Tumor Burden


  • 4-nitroquinolone-1-oxide
  • CD11b Antigen
  • HLA-DR Antigens
  • IL6 protein, human
  • ITGAM protein, human
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Quinolones
  • Reactive Oxygen Species
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • interleukin-6, mouse
  • 4-Nitroquinoline-1-oxide
  • Arg1 protein, mouse
  • Arginase