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

Myeloid-derived suppressor cells contribute to oral cancer progression in 4NQO-treated mice
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骨髓源性抑制细胞促进 4NQO 治疗小鼠口腔癌的进展

DOI:
10.1111/j.1601-0825.2011.01846.x
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发表时间:
2012-01-01
期刊:
影响因子:
3.8
通讯作者:
Liao, G-Q
Liao, G-Q
中科院分区:
医学3区
文献类型:
--
作者:
Chu, M.;Su, Y-X;Liao, G-Q

文献摘要

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目的:骨髓细胞异常增殖,尤其是髓源性抑制细胞(MDSCs)的扩增,越来越被认为是肿瘤逃避免疫监视的重要原因。本研究的目的是探讨这一特定群体的细胞在口腔癌progression.MATERIALS和METHODS的作用:4-硝基喹啉1-氧化物(4 NQO)诱导口腔癌C57 BL/6小鼠。采用苏木素和伊红染色法检查舌粘膜。流式细胞仪检测MDSCs在脾脏和外周血中的分布及脾脏T细胞亚群。免疫组化法检测舌组织中MDSCs的表达,实时荧光定量PCR法检测舌组织中NOS-2和ARG-1的表达。我们发现,在肿瘤进展过程中,在4 NQO治疗的小鼠的脾脏和外周血中观察到MDSC的频率显著增加,脾脏中MDSC的频率与系统性CD 3(+)CD 8(+)T细胞呈正相关。此外,4 NQO治疗的小鼠表现出显着更高的MDSCs浸润和ARG-1 mRNA水平在肿瘤situation.CONCLUSIONS:髓源性抑制细胞有助于口腔肿瘤的进展,并代表一个潜在的目标,为口腔癌的免疫治疗。
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.