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

Miao Fen Chen, Feng Che Kuan, Tzu Chen Yen, Ming Shian Lu, Paul Yang Lin, Yi Hsiu Chung, Wen Cheng Chen, Kuan Der Lee

Research output: Contribution to journalArticle

66 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8716-8728
Number of pages13
JournalOncotarget
Volume5
Issue number18
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

HLA-DR Antigens
Esophagus
Squamous Cell Carcinoma
Interleukin-6
4-Nitroquinoline-1-oxide
Neoplasms
Myeloid-Derived Suppressor Cells
Arginase
Myeloid Cells
Drinking Water
Reactive Oxygen Species
Animal Models
Esophageal Squamous Cell Carcinoma
Incidence
Therapeutics

Keywords

  • Esophageal SCC
  • IL-6
  • MDSC

ASJC Scopus subject areas

  • Oncology

Cite this

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. / Chen, Miao Fen; Kuan, Feng Che; Yen, Tzu Chen; Lu, Ming Shian; Lin, Paul Yang; Chung, Yi Hsiu; Chen, Wen Cheng; Lee, Kuan Der.

In: Oncotarget, Vol. 5, No. 18, 2014, p. 8716-8728.

Research output: Contribution to journalArticle

Chen, Miao Fen ; Kuan, Feng Che ; Yen, Tzu Chen ; Lu, Ming Shian ; Lin, Paul Yang ; Chung, Yi Hsiu ; Chen, Wen Cheng ; Lee, Kuan Der. / 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. In: Oncotarget. 2014 ; Vol. 5, No. 18. pp. 8716-8728.
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