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世界核心医学期刊文摘（胃肠病学分册） 2005年第8期1卷 47-48页

作者： unitt e Rushbrook S.M Marshall A G.J.M. Alexander 王铮 Box 157 Addenbro oke’s NHS Trust Hill’s RoadCambridge CB2 2QQ United Kingdom

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.

关键词：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

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肝移植后肿瘤淋巴细胞的浸润和肝细胞癌的复发

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世界核心医学期刊文摘（胃肠病学分册） 2006年第12期2卷 48-49页

作者： unitt e. Marshall A. Gelson W. G.J.M.Alexander 陈云茹 Department of Medicine University of Cambridge School of Clinical MedicineAddenbrooke's NHS TrustHills RoadCambridgeCB2 2QQUnited Kingdom

Background/Aims:Liver transplantation is an effective treatment for highly selected patients with hepatocellular carcinoma(HCC) ,but tumour recurrence remains an important cause of *** are few data on the relation between the recurrence of HCC and lymphocytic infiltration following liver ***:The tumour CD4+,CD8+,CD25+ and Foxp3+ lymphocyte infiltrate was assessed by immunohistochemistry in explant tissue of 69 patients who underwent liver transplantation for HCC between 1985 and *** data were analysed according to HCC recurrence and factors known to be associated with ***:Tumour size(Hazard ratio(95% CI:1.19(1.02,1.39) ,P = 0.03) ) ,vascular invasion(P = 0.02) ,lymphocyte infiltration(P = 0.02) and CD4 ∶ CD8 ratio(P = 0.001) were identified as significant univariate predictors of tumour *** multivariate analysis CD4 ∶ 8 ratio(P = 0.001) ,vascular invasion(P = 0.01) ,tumour size(P = 0.06) and reduced lymphocyte infiltration(P = 0.03) were significant independent predictors of *** presence of Foxp3+ T-lymphocytes was not predictive of recurrence,but was associated with vascular invasion(Fe = 9.02,P = 0.04) .Conclusions:The data support the hypothesis that immune responses are important in HCC and that the phenotype of infiltrating lymphocytes is informative regarding prognosis.

关键词：肝细胞癌肝移植血管浸润淋巴细胞浸润免疫组织化学法状况评估免疫反应单变量

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