髓样来源的抑制细胞在舌癌小鼠中的表达及意义

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。

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

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.