华西口腔医学杂志 ›› 2015, Vol. 33 ›› Issue (6): 575-580.doi: 10.7518/hxkq.2015.06.005

• 基础研究 • 上一篇    下一篇

髓样来源的抑制细胞在舌癌小鼠中的表达及意义

储眉1,廖贵清2,唐文1,周媛1,苏宇雄3,梁玉洁2   

  1. 1.广州市第八人民医院口腔科,广州510440;2.中山大学光华口腔医学院·附属口腔医院口腔颌面外科,广州510055;3.香港大学牙医学院口腔颌面外科,香港999077
  • 收稿日期:2015-04-23 修回日期:2015-09-06 出版日期:2015-12-01 发布日期:2015-12-01
  • 通讯作者: 廖贵清,教授,博士,E-mail:drliaoguiqing@hotmail.com
  • 作者简介:储眉,主治医师,博士,E-mail:gz8hcm@126.com
  • 基金资助:
    国家自然科学基金资助项目(81372884);广州市医药卫生科技项目(20141A011037)

Myeloid-derived suppressor cell expression and significance in peripheral blood and tongue lesions of mouse

Chu Mei1, Liao Guiqing2, Tang Wen1, Zhou Yuan1, Su Yuxiong3, Liang Yujie2   

  1. 1. Dept. of Stomatology, Guangzhou Number 8 People’s Hospital, Guangzhou 510440, China; 2. Dept. of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China; 3. Dept. of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong 999077, China)
  • Received:2015-04-23 Revised:2015-09-06 Online:2015-12-01 Published:2015-12-01

摘要: 目的 评价舌癌小鼠外周血和病变部位髓样来源的抑制细胞(MDSC)的变化及意义。方法 建立4NQO舌癌小鼠模型,观察MDSC细胞在外周血的表达,同时观察T细胞亚群的表达,评价MDSC细胞与T细胞亚群及CD4+/ CD8+比例变化的相关性。观察MDSC细胞在舌黏膜病变部位的表达,并检测舌组织精氨酸酶1(ARG-1)mRNA的表达。结果 4NQO小鼠外周血中MDSC比例随着肿瘤进展显著升高(P<0.01),外周血中MDSC比例与相应CD3+CD8+T细胞的比例呈正相关,与CD4+/CD8+比呈负相关关系。4NQO小鼠异常增生区域的MDSC细胞较正常对照组有所增加,在舌癌组织内及与正常组织的交界处,均浸润了大量的MDSC细胞,而且ARG-1 mRNA水平显著升高(P<0.01)。结论 MDSC细胞在舌癌组织和外周血中的扩增可能是肿瘤进展的重要原因。MDSC细胞可能成为口腔癌免疫治疗的潜在靶点。

关键词: 鳞状细胞癌, 髓样来源的抑制细胞, 免疫抑制

Abstract: Objective To explore the myeloid-derived suppressor cell (MDSC) expression in the peripheral blood and lesions of 4NQO-induced tongue carcinoma in mouse. Methods The established 4NQO mouse model was used to analyze the distribution of MDSC and T cell subsets in the peripheral blood by flow cytometry. The relations of MDSC with T cell subsets and CD4+/CD8+ changes were evaluated. The distribution of MDSC in the lesions of tongues was analyzed by immunohistochemistry, and the expression of arginase 1 (ARG-1) in tongue tissues was detected by real-time polymerase chain reaction. Results During tumor progression, a significant increase was observed in the frequency of MDSC in the peripheral blood of 4NQO treated mice (P<0.01). The frequency of MDSC was positively correlated with systemic CD3+CD8+T cells but negatively correlated with the CD4+/CD8+ ratio. Squamous cell carcinomas were extensively infiltrated with MDSC, whereas dysplastic area and normal tongue mucosa had only sparse MDSC infiltration. The majority of MDSCs were located in the stroma, particularly along the tumor invasive front. Moreover, 4NQO-treated mice showed significantly higher ARG-1 mRNA levels in the tumor site (P<0.01). Conclusion MDSC may contribute to oral tumor progression and represents a potential target for immunotherapy of oral cancer.

Key words: squamous cell carcinoma, myeloid-derived suppressor cell, immunosuppression

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