Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
Oral Dis. 2012 Jan;18(1):67-73. doi: 10.1111/j.1601-0825.2011.01846.x. Epub 2011 Aug 24.
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.
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.
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.
Myeloid-derived suppressor cells contribute to oral tumor progression and represent a potential target for immunotherapy of oral cancer.
异常的髓系细胞生成,特别是髓系来源的抑制细胞(MDSCs)的扩增,被认为是肿瘤逃避免疫监视的一个重要原因。本研究旨在探讨这一特定细胞群体在口腔癌进展中的作用。
采用 4-硝基喹啉 1-氧化物(4NQO)诱导 C57BL/6 小鼠发生口腔癌,苏木精-伊红染色观察舌黏膜变化。采用流式细胞术分析 MDSCs 在脾和外周血中的分布以及脾内 T 细胞亚群。免疫组织化学染色检测 MDSCs 在舌组织中的表达,实时 PCR 检测舌组织中精氨酸酶-1(ARG-1)和诱导型一氧化氮合酶-2(NOS-2)的表达。
我们发现,在肿瘤进展过程中,4NQO 处理小鼠的脾和外周血中 MDSCs 的频率明显增加,且脾中 MDSCs 的频率与系统性 CD3(+) CD8(+) T 细胞呈正相关。此外,4NQO 处理小鼠的肿瘤部位 MDSCs 浸润和 ARG-1 mRNA 水平明显升高。
髓系来源的抑制细胞促进口腔肿瘤的进展,可能成为口腔癌免疫治疗的一个潜在靶点。