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)-γ,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-β1 mRNA、INF-γ mRNA及IL-10 mRNA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-β1 mRNA、IL-10 mRNA、IFN-γ mRNA的表达分析结果显示,死亡组腋淋巴结中IL-10 mRNA阳性淋巴细胞密度显著高于5年以上生存组；虽然TGF-β1 mRNA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-10 mRNA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-γ mRNA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.

abstractsObjective 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 monoclonal 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 corresponding 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-γ 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 nodes between 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-β1 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+ cells (P ＜ 0.05),and the expression of TGF-β1 positive cells was also proportional to that of IL-10 mRNA positive cells (P ＜ 0.01).The expression of IFN-γ mRNA among these groups showed no significance (P ＞0.05).Conclusions Regulatory T cells may play important roles in inhibiting the host antitumor immunity,and the presence of increased regulatory T cells and Th2-secreting cells in paracortex with a proliferative pattern in the tumor draining lymph nodes implies that the paracortical proliferation of draining lymph nodes may not reflect positive antitumor effects.