原发性肝细胞癌微环境中CD4^＋CD25^＋调节性T细胞分布与局部免疫的关系

Relationship between disposition of CD4^ ＋ CD25^ ＋ regulated T cells in hepatocarcinoma （ HCC ） microenvironment and HCC local immunity

目的通过检测原发性肝细胞癌（hepatocellular carcinoma，HCC）局部肝癌组织和癌旁组织中T细胞亚群的分布情况，探讨在肝癌发生、发展过程中CD4^＋CD25^＋调节性T细胞与局部免疫状态的关系。方法54例肝癌组织和癌旁组织及10例正常肝组织用免疫组织化学S—P法标记CD4^＋T细胞、CD8^＋T细胞及CD4^＋CD25^＋调节性T细胞（CD4^＋CD25^＋Tr细胞），并对组织中CD4^＋CD25^＋Tr细胞与CD4^＋T、CD8^＋T及CD4^＋T／CD8^＋T值进行相关性分析。结果54例肝癌、癌旁组织中CD4^＋CD25^＋Tr细胞单个高倍视野平均数分别为5．6208±2．7235和3．8554±1．6018（P=0．001）；肝癌中CD4^＋CD25^＋Tr细胞数目与肿瘤大小、有无子灶有关，组间差异有显著性（P〈0．01）；肝癌中CD4^＋CD25^＋Tr数量与CD4^＋T细胞的数量以及CD4^＋T／CD8^＋T值呈显著负相关（r=-0．459，P=0．015；r=-0．563，P=0．011），而与浸润性CD8^＋T细胞的数量分布无关（r=-0．485，P=0．072）。结论在肝癌微环境中CD4^＋T淋巴细胞表达降低，CD4^＋CD25^＋Tr细胞表达增高，后者可能通过抑制CD4^＋T淋巴细胞的增殖来抑制肝癌局部免疫，从而促进肿瘤的进展以及侵袭或转移。

Objective To detect the disposition of T cells subset in tumor region and the marginal region of tumor（peritumor region）and study the relationship between CD4^＋ CD25^＋ regulated T cells（Tr） and local immunity in the process of hepatocarcinoma＇ s development. Methods CD4^＋ CD25^＋ Tr cells, CD4^＋ T cells and CD8^＋ T cells were detected in formalin - fixed paraffin - embedded tissues from 54 cases of HCC tissues and 10 cases of normal hepatocellular tissues by S - P immunohistochemical method. To analyze the level of their expression in these cases and relationships between CD4^＋ CD25^＋ Tr cells and CD4^＋ T cells, CD8^＋ T cells, CD^4＋ T/ CD8^＋ T. Results 54 patients with HCC had a higher number of CD4^＋ CD25^＋ Tr cells in tumor region （5. 6208 ± 2. 7235 ） than those of the peri - tumor region（ 3. 8554 ±1. 6018 ） （ P = 20. 001 ）. The number of CD4^＋ CD25^＋ Tr ceils in tumor tissue were correlated with the size of tumor and seed focus or not,the difference was signifieant（P 〈 0.01 ） ;The number of CD4^＋ CD25^＋ Tr cells in tumor tissue was negatively correlated with the number of infiltrated CD4^＋ T lympholeukocyte and the ratio of CD4^＋ T/CD8^＋ T （ r = - 0. 459, P = 20. 015 ; r = - 0. 563, P = 20.011 ） , and not with the distribution of invasion CD8^＋ T lympholeukocyte （ r= - 0.48, P = 20. 072 ）. Conclusions CD4^ ＋ CD25^＋ Tr cells is the main immunosupression cell in tumor microenvironment of HCC, they suppress proliferation of CD4^＋ T cell possibly so that tumor cells can escape immune surveillance and result in invasion and progression,thereby,contribute to the progression or metabasis of HCC, and can be used as an independent prognostic factor.