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非小细胞肺癌患者化疗前后免疫功能的改变
引用本文:郑惠如,金美玲,任涛,张镭,储以微.非小细胞肺癌患者化疗前后免疫功能的改变[J].复旦学报(医学版),2009,36(6):696-700.
作者姓名:郑惠如  金美玲  任涛  张镭  储以微
作者单位:复旦大学附属中山医院呼吸科,上海200032;同济大学附属东方医院呼吸科,上海200120;复旦大学上海医学院免疫学系,上海200032;复旦大学上海医学院分子医学教育部重点实验室,上海200032
基金项目:上海市重点学科建设项目,上海市自然科学基金项目 
摘    要: 目的 比较非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血CD3+T细胞、CD4+CD25high调节性T细胞(regulatory T cell,Treg cell)、γ-干扰素(interferon γ,IFN-γ)和白介素-12(interleukin-12,IL-12)与健康人的差异,并分析化疗前后CD4+CD25highTreg细胞、IFN-γ和IL-12的改变,探讨肺癌患者化疗前后免疫功能的改变。方法 选取NSCLC患者20例,健康志愿者20例为对照。分别抽取患者化疗前、化疗后3 d及7 d外周血3 mL,分离其外周血单个核细胞(peripheral blood mononuclear cell,PBMC),以流式细胞仪检测CD3+T细胞比例、CD4+CD25highTreg细胞比例(%),并取上清液检测IFN-γ和IL-12。结果 健康组CD3+T细胞比例为(61.52 ± 13.46)%,肺癌组化疗前CD3+T细胞比例为(55.15 ± 20.11)%,化疗后3 d、7 d分别为(57.73 ± 14.08)%和(62.79 ± 7.80)%。肺癌组化疗前与化疗后3 d、7 d比较,差异无统计学意义(P>0.05)。健康组CD4+CD25highTreg细胞的比例为(2.14 ± 0.85)%;肺癌组CD4+CD25highTreg细胞的比例在化疗前为(2.76 ± 0.53)%,较健康人明显升高(P<0.05);肺癌组CD4+CD25highTreg细胞的比例在化疗后3 d、7 d分别为(2.54 ± 0.57)%、(2.72 ± 0.29)%,较化疗前减少,而在3 d减少较7 d明显,各组比较,P<0.05。健康组 IFN-γ和IL-12分别为(34.36 ± 4.38)和(33.24 ± 4.36)pg/mL;肺癌组IFN-γ和IL-12在化疗前分别为(38.47 ± 5.04)和(34.82 ± 5.30)pg/mL,与健康组比较,差异无统计学意义(P>0.05)。肺癌组IFN-γ在化疗后3 d、7 d分别为(40.42 ± 5.66)和(39.27 ± 6.07)pg/mL,较化疗前有所增加,化疗后3 d和化疗前比较,P<0.05,但化疗后7 d和化疗前比较,P>0.05。肺癌组IL-12在化疗后3 d、7 d分别为(35.51 ± 5.03)和(38.62 ± 6.44)pg/mL,较化疗前有所增加,化疗后3 d和化疗前比较,P>0.05,化疗后7 d和化疗前比较,P<0.05。结论 化疗对肺癌患者机体的免疫环境可能具有优化作用,从而增强机体的抗肿瘤免疫应答。

关 键 词:非小细胞肺癌  外周血单核细胞  调节性T  细胞  IFN-γ  IL-12
收稿时间:2009-3-10

Immune function changes of non-small cell lung cancer patients after chemotherapy
ZHENG Hui-ru,JIN Mei-ling,REN Tao,ZHANG Lei,CHU Yi-wei.Immune function changes of non-small cell lung cancer patients after chemotherapy[J].Fudan University Journal of Medical Sciences,2009,36(6):696-700.
Authors:ZHENG Hui-ru  JIN Mei-ling  REN Tao  ZHANG Lei  CHU Yi-wei
Institution:Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Pulmonary Medicine, Eastern Hospital, Tongji University, Shanghai 200120, China; Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China; The Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 200032, China
Abstract:Objective To compare the proportion of CD3~+T cell and CD4~+CD25~(high) regulatory T cell (Treg cell) and the production of inferon γ ( IFN-γ) and interleukin-12 (IL-12) in peripheral blood mononuclear cells (PBMC) between patients with non-small cell lung cancer (NSCLC) and healthy people, and to analyze the changes of CD3~+T cell, CD4~+CD25~(high)Treg cell, IFN-γ and IL-12 of NSCLC patients before and after chemotherapy, so as to determine immune function changes of NSCLC patients caused by chemotherapy. Methods Twenty NSCLC patients and 20 healthy volunteers according to the including criteria were selected. Three mL of blood was drawn from NSCLC patients before chemotherapy (0 d), on the 3~(rd) day (3 d) and 7~(th) day (7 d) after chemotherapy. PBMC cells were separated from the blood samples. The proportions of CD4~+CD25~(high)Treg cell and CD3~+T cell (%) in PBMC were tested by FACS, and the IFN-γ and IL-12 (pg/mL) in the supernatants were also detected. Results The proportions of CD3~+T cell in NSCLC patients on 0, 3 and 7 d were (55.15±20.11)%,(57.73±14.08)% and (62.79±7.80)%,respectively, and there was no statistical difference between any two of these results. The proportion of CD4~+CD25~(high)Treg cell in healthy volunteers was (2.14±0.85)%, while that of NSCLC patients was (2.76±0.53)% on 0 d with statistical difference compared to the healthy volunteers (P<0.05). The CD4~+CD25~(high)Treg cell proportion (%) of NSCLC patients on 3 d and 7 d were (2.54±0.57)% and (2.72±0.29)%, respectively, which were both significantly lower than that of 0 d. On 3 d it was even much lower than that on 7 d (P<0.05). IFN-γ and IL-12 of NSCLC patients on 0 d were (34.36±4.38) pg/mL and (33.24±4.36) pg/mL, and no statistical difference was observed when compared with (34.36±4.38) pg/mL and (33.24±4.36) pg/mL in the healthy volunteers. On 3 d and 7 d, IFN-γ of NSCLC patients were (40.42±5.66) pg/mL and (39.27±6.07) pg/mL, respectively, and both were higher than that on 0 d (P<0.05); IL-12 of NSCLC patients were (35.51±5.03) pg/mL and (38.62±6.44) pg/mL, also both were higher than that on 0 d (P<0.05). Conclusions This study suggests that chemotherapy can improve immune functions of NSCLC patients, and may reinforce the anti-tumor immune response.
Keywords:IL-12
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