原发性肝细胞癌局部微环境中叉头框蛋白P3＋naturalT细胞的变化  

FOXP3 ＋ natural T cells in local microenvironment of primary hepatocellular carcinoma

作　　者：李小凤[1] 徐文贵[1] 戴东[1] 宋秀宇[1] 朱磊[1] 刘建井[1] 朱湘[1] 马文超[1] 

机构地区：[1]天津医科大学肿瘤医院分子影像及核医学诊疗科国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室,300060

出　　处：《中华肝胆外科杂志》2015年第11期741-745,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：天津市卫生局科技基金项目（2013KZ088）;天津医科大学科学基金项目（2013KYQ07）

摘　　要：目的探讨原发性肝细胞癌肿瘤组织局部叉头框蛋白P3＋（FOXP3＋）naturalT细胞（CD3＋CD56＋）数量、表型和功能的变化。方法通过流式细胞表面染色和胞内因子染色检测肝癌组织naturalT细胞数量、细胞表型、细胞因子表达分泌等方面的变化。结果与癌旁组织相比，肝癌组织（n=16）局部浸润的naturalT细胞比例明显降低（6．32±1．00比17．16±1．80，P〈0．05），而与正常志愿者（n=11）相比，肝癌患者外周血单核细胞（PBMC）中的naturalT细胞比例上没有显著差异（5．95±0．91比5．76±1．16，P〉0．05）。在肝癌组织局部浸润的naturalT细胞存在有与传统T细胞（CD3＋CD56-）比例相当的FOXP3表达阳性细胞群（21．96±5．28比15．00±2．22，P〉0．05）。在细胞表型上，FOXP3阳性naturalT细胞主要集中在CD4＋CD8-细胞群，并且高比例表达CD45RO、CD25和CTLA-4等细胞活化标志。在细胞功能上，FOXP3阳性naturalT细胞不再表达分泌IFN-γ和perforin等免疫效应分子。结论肝癌癌组织局部浸润的naturalT细胞比例明显降低，并使得naturalT获得FOXP3的阳性表达。FOXP3＋naturalT细胞具有与调节性T细胞相类似的特异表型和细胞因子分泌特性。Objective To study natural T cells （CD3 ＋ CD56 ＋） on cell quantity, phenotype and function in tumor infiltrating lymphocytes （ TILs ） of primary hepatocellular carcinoma （ HCC ）. Methods To detect cell quantity, cell phenotype and cytokine secretion of natural T cells in patients with primary hepatocellular carcinoma through flow cytometric surface and intracellular staining. Results There was a sharp decrease in the percentage of natural T cells in TILs when compared to non-tumor infiltrating lymphocytes （NILs） in patients with HCC （n = 16; 6. 32 ± 1.00 vs 17. 16 ±1.80, P 〈0. 05）. However, the proportion of natural T cells in the peripheral blood of patients with HCC was similar to normal volunteers （ n = 11 ; 5.95 ± 0. 91 vs 5.76 ± 1.16, P 〉0. 05）. Furthermore, there was a comparable percentage of FOXP3 ＋ cells in the natural T cells when compared to the conventional T cells （ CD3 ＋ CD56 - ） in TILs （ 21.96 ± 5.28 vs 15.00 ± 2. 22, P 〉 0. 05 ）. FOXP3 ＋ natural T cells had a specific phenotype that was characteristic of CD4 ＋CD8-, CD25 ＋ , CD45RO ＋ and CTLA-4 ＋. Functional assay and analysis demonstrated that FOXP3 ＋ natural T cells no longer expressed and secreted effectors such as IFN-γ and perforin. Conclusions Hepatocellular carcinoma gave rise to a significant decrease in the percentage of natural T cells in TILs when com- pared with NILs. A new FOXP3 ＋ natural T cell subset naturally occurring in the TILs of patients with HCC with similar phenotypic and functional characteristics to regulatory T cells had been discovered.

关 键 词：原发性肝细胞癌 NATURAL T细胞 调节性T细胞 免疫抑制 自然杀伤细胞 

分 类 号：R392.4[医药卫生—免疫学]