人乳腺癌组织及局部引流淋巴结中调节性T细胞分析  

Tumor infiltrating regulatory T cells in human breast cancer and associated draining lymph nodes：an in-situ ana!ysis

作　　者：王鸿雁[1] 史秦峰[1] 孙颖[1] 何建军[1] 王一理[2] 

机构地区：[1]西安交通大学第一附属医院肿瘤研究中心,710061 [2]西安交通大学生命科学与技术学院癌症研究所,710061

出　　处：《中华病理学杂志》2013年第2期95-100,共6页Chinese Journal of Pathology

摘　　要：目的研究乳腺癌组织及腋淋巴结中浸润的调节性T细胞的数量和状态，并与乳腺癌临床病理特征相比较，探讨其意义。方法对74例乳腺癌原发灶及所切除的腋淋巴结进行病理分型和临床病理分期。采用免疫组织化学EnVision法，以单克隆抗体CD25和Foxp3标记肿瘤局部及淋巴结中调节性T细胞，并分析其表达情况。原位杂交法检测肿瘤局部引流淋巴结淋巴细胞的干扰素（IFN）-1，白细胞介素（IL）-10和转化生长因子（TGF）-β1等细胞因子mRNA表达情况。结果淋巴结中CD25^＋细胞和Foxp3^＋细胞多分布于副皮质区，且均以副皮质区增生型淋巴结反应分布较多。TGF-β1mRNA、INF-γmRNA及IL-10mRNA阳性细胞主要分布于淋巴结副皮质区，亦以副皮质区增生型分布较多。39例有转移者的受累淋巴结Foxp3^＋和CD25^＋细胞密度显著高于未受累淋巴结（23．5比17．3，23．8比15．5；P〈0．05），有转移死亡组与有转移生存组腋淋巴结中Foxp3^＋和CD25^＋细胞密度相比差异无统计学意义（P〉0．05）。对24例患者腋淋巴结细胞因子TGF-β1mRNA、IL-10mRNA、IFN-γmRNA的表达分析结果显示，死亡组腋淋巴结中IL-10mRNA阳性淋巴细胞密度显著高于5年以上生存组；虽然TGF-β1mRNA阳性淋巴细胞密度在死亡组高于生存组，但差异无统计学意义（P〉0．05）。腋淋巴结中TGF-β1、IL-10mRNA表达与CD25’和Foxp3^＋呈正相关（P〈0．05）。TGF-β1与IL-10呈正相关（P〈0．01）。IFN-1mRNA表达与各指标间均无显著相关性（P〉0．05）。结论调节性T细胞在抑制荷瘤宿主抗肿瘤免疫反应中可能发挥重要作用；调节性T细胞和Th2因子分泌细胞主要见于副皮质区增生的局部引流淋巴结，淋巴结副皮质区增生性免疫组织反应未必反映正性抗瘤效应。Objective To retrospectively analyze the quantity and status of the tumor infiltrating regulatory T lymphocytes in breast cancer and the draining lymph nodes, and to elucidate the clinical pathologic significance. Methods Seventy-four breast cancer samples with excised axillary lymph nodes were typed and staged histopathologically. The regulatory T lymphocytes were labeled by immunohistochemistry using EnVision method with the monoelonal antibodies against CD25 and Foxp3, and the immunophenotype was analyzed. In addition, the expression of IFN-γ, IL-10 and TGF-β1 mRNA in lymphocytes of lymph nodes draining the tumors was detected by in situ hybridization with the cmTesponding specific oligo nucleaic acid probes. Results The number of CD25 ＋ Foxp3 ＋ T cells infiltrating the interstitium was much higher than that in the parenchymal tissue of the cancer. In the tumor draining lymph nodes, CD25 ＋cells and Foxp3＋ cells were predominantly distributed in the paracortex with a proliferative pattern. TGF-β1, INF-3, and IL-10 mRNA positive cells showed a similar distribution pattern in the draining lymph nodes. Among the 39 cases with metastatic disease, the lymph nodes with metastases showed a much higher number of CD25 ＋ Foxp3 ＋ cells than that without metastases （23. 5 vs 17, 3 and 23. 8 vs 15. 5 ; P 〈 0.05）. However, there was no difference in the density of Foxp3＋ CD25＋ cells in the draining lymph nodesbetween the death and survival groups （ P 〉 0.05 ）. Cytokine expression of TGF-β1, IL-10 and IFN-γ mRNA in the lymphocytes of draining lymph nodes in 24 cases showed that there were more IL-10 mRNA positive cells in the dead patients than that in the survived patients. A similar trend was observed for TGF-I3! mRNA positive cells but the difference was not statistically significant （P 〉 0. 05 ）. The expression rate of TGF-β1 and IL-10 mRNA in the draining lymph nodes was proportional to that of CD25 ＋ and Foxp3 ＋ ceils （P 〈 0.05）, and the expression of TGF-β1 positive c

关 键 词：乳腺肿瘤 肿瘤微环境 原位杂交 T淋巴细胞 调节 

分 类 号：R737.9[医药卫生—肿瘤]