Myeloid-derived suppressor cells contribute to oral cancer progression in 4NQO-treated mice

Authors


Gui-qing Liao, DDS, PhD, Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Xi Road, Guangzhou 510055, China. Tel: 0086 20 83862531,, Fax: 0086 20 83822807, E-mail: drliaoguiqing@hotmail.com

Abstract

Oral Diseases (2011) 18, 67–73

Objective:  Abnormal myelopoiesis especially the expansion of myeloid-derived suppressor cells (MDSCs) is increasingly recognized as an important reason for the escape of tumor from immune surveillance. This study aims to investigate the role of this specific population of cells in oral cancer progression.

Materials and Methods:  4-Nitroquinoline 1-oxide (4NQO) was used to induce oral cancer in C57BL/6 mice. The tongue mucosa was examined by hematoxylin and eosin staining. The distribution of MDSCs in the spleen and peripheral blood and T cell subsets in the spleen was analyzed by flow cytometry. The expression of MDSCs in the tongue tissues was investigated by immunohistochemical staining, and the expression of arginase-1 (ARG-1) and NOS-2 in the tongue tissues was detected by real-time PCR.

Results:  We found that during tumor progression, significantly increased frequency of MDSCs was observed in the spleens and peripheral blood of 4NQO-treated mice, and the frequency of MDSCs in the spleens was positively correlated with systemic CD3+CD8+ T cells. Moreover, 4NQO-treated mice showed significantly higher MDSCs infiltration and ARG-1 mRNA level in the tumor site.

Conclusions:  Myeloid-derived suppressor cells contribute to oral tumor progression and represent a potential target for immunotherapy of oral cancer.

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