肝细胞癌微环境中CD4^＋CD25^＋调节性T细胞的分布及其临床病理意义

Clinicopathological significance of distribution of Treg in microenvironment of hepatocellular carcinoma

目的研究CD4^＋CD25^＋调节性T细胞（Treg）与肝细胞癌（HCC）临床病理之间的关系；探讨其在评价HCC侵袭性和癌症进展以及预后中的价值。方法用双重酶标免疫组织化学的方法测定52例HCC组织及癌旁组织中Treg数量分布状况。分析其临床病理学资料，研究在HCC微环境中Treg数量分布与其各项临床病理学指标间的关系。结果8例正常肝组织中未发现Treg分布，52例HCC病人的肝癌及癌旁组织标本中，在HCC组织中Treg数量明显高于癌旁组织，差异有显著意义。HCC组织的Treg数量与病人性别、年龄、肝硬化、病理学分级、包膜、术前AFP浓度无显著关系（P〉0．05），而与肿瘤的大小、癌栓、子灶、TNM分期有显著关系。25例小肝癌组和27例大肝癌组Treg细胞单个高倍视野平均数分别为7．1440±1．8535、8．0815±1．5122，两组比较在统计学上有显著差异（P〈0．001）；14例有血管癌栓组和38例无血管癌栓组Treg细胞单个高倍视野平均数分别为8．1143±2．4487、7．4526±1．8794，两组比较差异有统计学意义（P〈0．05，P=0．014）；19例癌周有子灶组和33例癌周无子灶组Treg细胞单个高倍视野平均数分别为8．2211±2．4516、7．2909±1．8217，两组比较在统计学上有显著差异（P〈0．001）；不同临床病理分期18例Ⅰ期组、22例Ⅱ期组和12例Ⅲ期组中Treg细胞单个高倍视野平均数分别为6．7333±1．5980、7．8818±2．4171、8．5167±2．2480，在统计学上有显著差异（P〈0．001）。结论肝细胞癌微环境中Treg数量分布与肿瘤大小、血管癌栓、子灶，和临床分期有明显关系，而与其它指标无显著关系。HCC微环境中Treg数量与肝癌的侵袭、进展以及预后有密切关系，HCC微环境中Treg数量增多可以作为判断HCC侵袭性、进展以及预后的一个潜在重要指标。除去或减少肝癌微环境中的Treg细胞有可能提高肿瘤的免疫治疗效果。

Objective To study the relation of Treg cells to clinicopathology of hepatocellular carcinoma （HCC） and explore its value for evaluating invasion and progression of the tumor. Methods The double enzyme-labeled immunohistochemistry was used to detect the expression of Treg cells in samples of juxtacancerous and HCC tissues from 52 patients. The clinicopathological data of the 52 patients were analyzed. Meanwhile, the relationship between the clinicopathological data and number of Treg cells was determined. Results There were no Treg cells in the 8 cases of benign liver tissues. The average number of Treg cells in every visual field of the juxtacancerous and HCC tissues was 5. 1654±1. 6718 and 7. 6308±2. 8368, respectively （P=0.000）. The number of Treg cells in HCC was related to tumor size, vascular invasion and satellite nodules. The average number of Treg cells in every visual field was significantly higher in the 14 cases with vascular invasion than in the 38 without （8. 1143±2. 4487 vs. 7. 4526±1. 8794, P=0. 014）. This average number was markedly higher in the 19 patients with satellite nodules than in the 33 without （8. 2211±2. 4516 vs. 7. 2909±1. 8217, P= 0. 000）. It was remarkably lower in the 25 cases of small HCC （≤5 cm） than in the 27 of big or large HCC （〉5 cm） （7.1440±1. 8535 vs. 8. 0815±1.5122, P=0.000）. Furthermore, it was 6. 7333±1.5980, 7. 8818±2. 4171 and 8. 5167±2. 2480 in 18 cases of stage Ⅰ , 22 of stage Ⅱ and 12 of stage Ⅲ , respectively （P=0. 000）. Conclusions The number of Treg cells in microenvironment of HCC is significantly correlated to tumor size, vascular invasion, satellite nodules and TNM grade, which indicates that the Treg cells can promote invasion and progression of HCC. Functional deletion of tumorinfiltrating Treg cells could enhance tumor-specific immunotherapy.