Increase of CD4+ CD25+ regulatory T-cells in the liver of patients with hepatocellular carcinoma
Increase of CD4+ CD25+ regulatory T-cells in the liver of patients with hepatocellular carcinoma
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DOI：
10.1016/j.jhep.2006.01.036
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发表时间：
2006-08-01
影响因子：
25.7
通讯作者：
Aoyagi, Yutaka
中科院分区：
文献类型：
--
作者：
Yang, Xiu Hua;Yamagiwa, Satoshi;Aoyagi, Yutaka
背景/目的：对肿瘤特异性抗原的免疫应答通常无法控制恶性细胞的生长和扩散。越来越多的证据表明，CD 4（+）CD 25（+）调节性T细胞的抑制作用至少部分负责免疫介导的肿瘤细胞清除的失败。将肝癌组织分为肿瘤边缘区（瘤周区）和远离肿瘤的非肿瘤区。通过流式细胞术和免疫组织化学定量血液和肝脏中的CD 4（+）CD 25（+）T细胞，并确定其对T细胞增殖和活化的影响。我们发现在肿瘤周围区域，CD 4（+）CD 25（+）T细胞的比例和绝对数量都有显著增加，但在未受影响的区域则没有（9.5 ± 4.5 vs. 4.6 ± 2.8%，P = 0.011）。从肿瘤周围区域分离的C134（+）CD 25（+）T细胞显示出调节性T细胞的表型标志物，并表达Foxp 3 mRNA。肿瘤周围CD 8（+）T细胞与肿瘤周围CD 4（+）CD 25（+）T细胞呈负相关（P < 0.001）。结论：HCC边缘区的CD 4（+）CD 25（+）T细胞可能在控制CD 8（+）细胞毒性T细胞活性中起关键作用，从而促进HCC的进展。(c)2006年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: The immune response to tumor-specific antigens is typically unable to control the growth and spread of malignant cells. Accumulating evidence indicates that the suppressive effects of CD4(+) CD25(+) regulatory T-cells are at least partially responsible for the failure of immune-mediated elimination of tumor cells.Methods: We have studied 25 patients with hepatocellular carcinoma (HCC). The liver tissues with HCC were separated into the marginal region of tumor (peri-tumor region) and the non-tumor region distant from the tumor. CD4(+) CD25(+) T-cells were quantified in the blood and the liver by flow cytometry and immunohistochemistry, and their effect on T-cell proliferation and activation was determined.Results: We found a significant increase in both the proportion and absolute numbers of CD4(+) CD25(+) T-cells in the peri-tumor regions, but not in unaffected areas (9.5 4.5 vs. 4.6 2.8%, P = 0.011). C134(+) CD25(+) T-cells isolated from peri-tumor regions displayed phenotype markers characteristic of regulatory T-cells, and expressed Foxp3 mRNA. CD8(+) T-cells in peri-tumor regions were inversely proportional to CD4(+) CD25(+) T-cells in the same region (P < 0.001). Moreover, isolated C134(+) CD25(+) T-cells inhibited autologous C138(+) T-cell proliferation.Conclusions: Our results suggest that CD4(+) CD25(+) T-cells in the marginal region of HCC may play a critical role in controlling CD8(+) cytotoxic T-cell activity and, thereby, contribute to the progression of HCC. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.