肝细胞性肝癌中淋巴细胞的浸润:T调节细胞的作用

作     者：Unitt E Rushbrook S.M Marshall A G.J.M. Alexander 王铮 

作者机构：Box 157 Addenbro oke’s NHS Trust Hill’s RoadCambridge CB2 2QQ United Kingdom 

出 版 物：《世界核心医学期刊文摘（胃肠病学分册）》 (Core Journals in Gastroenterology)

年 卷 期：2005年第1卷第8期

页      面：47-48页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：肝细胞性肝癌 T调节细胞 中淋巴细胞 肿瘤浸润 循环血液 流式细胞技术 转化生长因子 激活途径 特异性免疫治疗 免疫反应 

摘      要：Hepatocellular carcinoma (HCC) has a poor prognosis with limited therapeutic o ptions. We propose that local immune responses in patients with HCC are held in check by tumorinfiltrating CD4+CD25+T-regulatory lymphocytes(Treg cells),which suppress the activity and proliferation of effector CD4+and CD8 +T cells. The phenotype and cell cycle status of tumor-infiltrating lymphocyte s (TILs) in HCC were analyzed via immunohistochemistry of sections from patients undergoing surgery for HCC and via flow cytometry of peripheral blood mononucle ar cells and TILs isolated from patients with *** and tumor-infiltr ating T-cell function and activation status were assessed via proliferation and flow cytometry. More than 96%of TILs were quiescent as measured via Mcm-2 or Ki-67 expression, while less than 10%of CD8+T cells expressed perform or gran zyme B. CD4+CD25+Treg cells comprised 8.7%(1.4-13.8) of TILs and always exce ed- ed the proportion in distant nontumor tissue (2.4%[1.5-5.6]; P = .014). Treg cells isolated from HCC suppressed proliferation of autologous circulating CD4 +CD25-cells and perforin expression and proliferation of autologous CD8+T cel ls. The proportion of circulating Treg cells in patients with HCC was similar in healthy controls(7.2%[1.2-23.3] and 9.2%[1.6-30.2], respectively), but the proportion of circulating Treg cells that were also transforming growth factor β1+was elevated in HCC compared with controls(55.5%[8.2-73.9] and 2.0%[0-4 .9], respectively; P = .003). In conclusion, TILs are compromised and contain a subpopulation of suppressive CD4+ CD25+Foxp3+Treg cells. Functional deletion of tumor-infiltrating Treg cells could enhance tumor specific immunot- herapy.