非小细胞肺癌患者引流区淋巴结中CD_4^+CD_(25)^+调节性T细胞的检测及临床意义  

Clinical significance of CD_4^+CD_(25)^+ regulatory T-Cells detection in tumor-draining lymph nodes of non-small cell lung cancer patients

作　　者：苏延军[1] 任凯[1] 李慧 任秀宝 王长利[1] 

机构地区：[1]天津医科大学附属肿瘤医院肺部肿瘤科,300060 [2]天津市肿瘤防治重点研究室

出　　处：《中华肿瘤杂志》2007年第12期922-926,共5页Chinese Journal of Oncology

摘　　要：目的分析非小细胞肺癌(NSCLC)患者引流区淋巴结中CD4+CD25+调节性T细胞在淋巴结局部免疫抑制状态的形成以及在肺癌发生发展中的作用。方法手术切除53例NSCLC患者引流区淋巴结,采用双标记的间接免疫荧光法检测CD4+CD25+调节性T细胞数量,实时荧光定量逆转录-聚合酶链反应(RT-PCR)法检测细胞因子TGF-β1、IL-10的表达水平,常规免疫组化方法检测CD8+T细胞的数量。结果NSCLC患者引流区转移淋巴结中,CD4+CD25+调节性T细胞(28.80%±8.06%)明显高于未转移淋巴结(15.48%±4.66%,P<0.01)。随肺癌的进展,引流区淋巴结中CD4+CD25+调节性T细胞数量增多。在转移的纵隔淋巴结(N2)和肺内淋巴结(N1)中,CD4+CD25+调节性T细胞数量分别为32.58%±7.52%和22.76%±4.67%(P<0.01)。在进展期(Ⅲ)和早期(Ⅰ+Ⅱ)NSCLC患者引流区淋巴结中,CD4+CD25+调节性T细胞数量分别为30.42%±7.47%和16.22%±4.88%(P< 0.01)。NSCLC患者引流区淋巴结中的CD4+CD25+调节性T细胞数量与其自身的CD8+T细胞的数量呈负相关(r=-0.756,P<0.001)。在NSCLC患者引流区淋巴结中,CD4+CD25+调节性T细胞数量与抑制性细胞因子TGF-β1和IL-10的表达水平呈正相关(TGF-β1:r=0.645,P<0.001;IL-10:r=0.769,P<0.001)。结论NSGLC患者引流区淋巴结的CD4+CD25+调节性T细胞数量与肺癌的发展密切相关。一方面,检测肺癌患者引流区淋巴结的免疫状况为评价NSCLC患者疾病的进展程度和预后提供了一个新的免疫学指标;另一方面,在NSCLC的生物治疗中,控制CD4+CD25+调节性T细胞数量,阻断其发挥免疫抑制作用,具有广阔的临床应用前景。Objective To evaluate the distribution of CD4＋CD25＋ regulatory T-cells （T-regs） in tumor-draining lymph nodes （ TDLN） in patients with non-small cell lung caner （ NSCLC） , and to investigate the effect of CD4＋ CD25＋ T regulatory cells on the immune status of TDLN and the progression of NSCLC. Methods Regional tumor-draining lymph nodes of 53 NSCLC patients were resected during the operation. The percentage of CD4＋ CD25＋ T-regs as a subset of CD4＋ T cells and CD8＋ T cells were detected by immunofluorescence and regular immunohistochemistry, respectively. The level of cytokines TGF-β1 and IL-10 was detected by real time quantitative RT-PCR. Results CD4＋ CD25＋ T-regs in tumor-infiltrating lymph nodes from the patients with NSCLC accounted for 28. 80%±8. 06% of total CD4＋ T cells, and were significantly increased comparing with that （15.48%±4.66% ） in the tumor-free lymph nodes （P 〈0.01）. The percentage of CD4＋ CD25＋ T-regs in TDLN of NSCLC patients was negatively correlated with the amount of CD8＋ T cells within the lymph nodes（r = -0. 756, P 〈0.001） , but positively correlated with the level of TGF-β1 （r=0. 645, P〈0. 001） and IL-10（r = 0. 769, P 〈 0. 001）. It also increased as NSCLC getting progressed, which was 30.42%±7.47% in stageⅢversus 16. 22%±4. 88% in stageⅠandⅢ; 32. 58%±7.52% in N2 versus 22. 76%±4. 67% in N1, with a significant difference between the two groups, respectively（P 〈 0. 01 ）. Conclusion The population of CD4＋CD25＋ T regulatory cells in tumor-draining lymph nodes in patients with non-small cell lung caner is positively correlated with the progression and infiltration of lung cancer, which might provide new immunologic method to evaluate the progression and prognosis of non-small cell lung caner. The outcomes of biotherapy for NSCLC may be improved in the future through regulating the CD4＋ CD25＋ T regulatory cells.

关 键 词：非小细胞肺癌 肿瘤引流区淋巴结 CD4+CD25+调节性T细胞 TGF-Β IL-10 免疫抑制 

分 类 号：R734.2[医药卫生—肿瘤]