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

doi:10.18632/oncotarget.2368

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.

Highlights

Esophageal cancer is an aggressive upper gastrointestinal malignancy that generally present as a locally advanced tumor that requires multimodal treatment [1]
We investigated the potential role of Myeloid-derived suppressor cells (MDSCs) in tumor progression using a 4-nitroquinoline 1-oxide (4-NQO)induced esophageal tumor animal model, which could study the effects of immunity on esophageal cancer in immunocompetetnt mice [16]
peripheral blood mononuclear cells (PBMC) were isolated from esophageal cancer patients or healthy donors and were stained for detecting MDSCs using fluorochromelabelled antibodies targeting CD14, CD11b, and human leukocyte antigen (HLA)-DR

Summary

Introduction

Esophageal cancer is an aggressive upper gastrointestinal malignancy that generally present as a locally advanced tumor that requires multimodal treatment [1]. Identification of the potential molecular markers for predicting the treatment response and understanding the molecular mechanisms underlying aggressive tumor growth is important for the effective management and prognosis of esophageal cancer. Abundant epidemiological data revealed a strong correlation between inflammation and the incidence of cancers [2, 3]. Chronic inflammation contributes to tumor initiation and progression via both non-immune and immune mechanisms [4]. Myeloid-derived suppressor cells (MDSCs) are an immature population of myeloid cells that are thought to be an important subset of cells that contribute to an immunosuppressive tumor microenvironment [6,7,8], and significantly increased in number in cancer patients. A significant correlation was reported among circulating www.impactjournals.com/oncotarget

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