The impact of CD4+CD25+ T cells in the tumor microenvironment of hepatocellular carcinoma
The impact of CD4+CD25+ T cells in the tumor microenvironment of hepatocellular carcinoma
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DOI：
10.1016/j.surg.2011.07.029
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发表时间：
2012-02-01
期刊：
影响因子：
3.8
通讯作者：
Wang, Chao-Ching
中科院分区：
文献类型：
--
作者：
Lee, Wei-Chen;Wu, Ting-Jung;Wang, Chao-Ching
背景肝细胞癌（Hepatocellular carcinoma，HCC）是最常见的肝癌，由于肝癌经常复发，治疗效果往往不理想。免疫因素可能与肝癌的复发有关;然而，这种可能性很少被提及。30例肝癌切除术患者根据肝癌直径分为3组：A组（n = 8），直径3cm和5cm。分析外周血、非肿瘤肝组织和HCC中的T淋巴细胞。3组间外周血和非肿瘤肝组织中CD 4 + T细胞中CD 25+的比例无显著性差异。与A组患者相比，C组患者肿瘤组织中的CD 25（+）细胞增加（范围，6-41%;中位数，22.9%; P = 0.003）。肿瘤组织中CD 4 + T细胞中CD 25（+）的比例与肿瘤大小呈正相关（r = 0.556）。这些CD 4（+）CD 25（+）淋巴细胞产生转化生长因子-β和干扰素-γ，但不产生白细胞介素-10，并且对平板包被的单克隆抗体（抗CD 3/抗CD 28）无反应性。这些抗体的特征与调节抗体的特征相当。T细胞。当浸润淋巴细胞（包括CD 4（+）CD 25（+）T细胞）加入自体肿瘤裂解物致敏的树突状细胞激活的混合淋巴细胞反应中时，淋巴细胞的增殖受到抑制。肿瘤微环境中CD 4（+）CD 25（+）T细胞的增加与肿瘤大小相关。这些CD 4（+）CD 25（+）调节性T细胞似乎抑制了树突状细胞激活的免疫应答。（Surgery 2012;151：213-22.）
Background. Hepatocellular carcinoma (HCC) is the most common liver cancer Therapeutic results are usually unsatisfactory because liver tumors recur often. Immunologic factors may be related to the recurrence of HCC; however; this possibility is mentioned only rarely.Methods. Thirty HCC patients undergoing hepatectomies were divided into 3 groups according to the diameters of their HCCs: group A (n = 8), diameter 3 cm and 5 cm. T-lymphocytes from peripheral blood, nontumor liver tissue, and the HCC were analyzed.Results. The percentage of CD25(+) in the CD4(+) T cells did not differ between the peripheral blood and the nontumor liver tissue among the 3 groups. CD25(+) cells were increased in the tumor tissue in group C patients (range, 6-41%; median, 22.9%; P = .003), compared to group A patients. The percentage of CD25(+) in the CD4+ T cells in tumor tissue was positively correlated with tumor sizes (r = 0.556). These CD4(+) CD25(+) lymphocytes produced transforming growth factor-beta and interferon-gamma but not interleukin-10, and were anergic to plate-coated monoclonal antibodies (anti-CD3/anti-CD28). The characteristics of these antibodies were comparable to those of regulatory. T cells. When the infiltration lymphocytes including CD4(+) CD25(+) T cells were added to the mixed lymphocyte reaction activated by autologous tumor lysate-pulsed dendritic cells, the proliferation of lymphocytes was inhibited.Conclusion. The increase of CD4(+) CD25(+) T cells in the tumor microenvironment correlates with tumor sizes. These CD4(+) CD25(+) regulatory T cells appeared to suppress the immune response activated by dendritic cells. (Surgery 2012;151:213-22.)