[1]刘康栋),秦珍珠)),路静),等.高转移结肠癌细胞微环境对人树突状细胞功能的影响*[J].郑州大学学报(医学版),2009,(06):1146-1150.
 LIU Kangdong),QIN Zhenzhu)),LU Jing),et al.Effects of highly metastatic colon carcinoma cell microenvironment on function of human dendritic cell[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):1146-1150.
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高转移结肠癌细胞微环境对人树突状细胞功能的影响* ()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2009年06期
页码:
1146-1150
栏目:
论著
出版日期:
2009-11-01

文章信息/Info

Title:
Effects of highly metastatic colon carcinoma cell microenvironment on function of human dendritic cell
作者:
刘康栋1)秦珍珠1)2)路静1)杨洪艳1)黄幼田1)郑智敏1)赵明耀1)董子明1)#
1)郑州大学基础医学院病理生理学教研室 郑州 4500012)商丘市第一人民医院病理科 商丘 476100
Author(s):
LIU Kangdong1)QIN Zhenzhu1)2)LU Jing1)YANG Hongyan1)HUANG Youtian1)ZHENG Zhimin1)ZHAO Mingyao1)DONG Ziming1)
1)Department of Pathophysiology,College of Basic Medical Sciences,Zhengzhou University,Zhengzhou 4500012)Department of Pathology,the First People’s Hospital of Shangqiu,Shangqiu 476100
关键词:
结肠癌树突状细胞肿瘤微环境SW620细胞
Keywords:
colon carcinomadendritic celltumour microenvironmentSW620 cell
分类号:
R735.3
摘要:
探讨高转移结肠癌细胞SW620分泌的可溶性细胞因子营造的微环境对人单个核细胞来源的树突状细胞(DC)分化发育的影响,为DC疫苗在结肠癌患者中的临床应用提供依据。方法:密度梯度离心法分离人外周血单个核细胞,加入含重组人粒细胞巨噬细胞集落刺激因子和重组人白细胞介素4的RPMI 1640培养液诱导培养,第2天对照组同前培养,实验组在此基础上加入SW620条件培养基,均隔天半量换液,第4天加入超声破碎法制备的SW620抗原,第6天加入脂多糖。第8天收集对照组正常成熟DC和实验组肿瘤相关DC(TADC)。显微镜观察其形态,流式细胞仪检测其免疫表型,RTPCR检测CD1a mRNA的表达,混合淋巴细胞反应及体外杀伤活性实验检测其刺激T细胞增殖及杀伤能力。结果:TADC与正常成熟DC相比,细胞形态明显受到抑制。流式细胞仪检测PBMC、正常DC及TADC CD86及CD1a分子阳性率,差异均有统计学意义(F分别为46.95及19.09,P<0.001)。与正常DC比较,TADC CD86分子阳性率由(68.56±8.04)%降为(42.41±10.87)%,CD1a分子阳性率由(55.71±12.12)%降为(26.60±12.03)%(P均<0.05);CD1a基因表达降低,体外刺激T细胞增殖[(112.53±7.16)% vs. (91.26±6.62)%]及杀伤能力[(62.42±0.57)% vs. (50.37±2.21)%]均下降(t分别为6.17、17.41,P均<0.001)。结论:SW620条件培养基所营造的微环境对DC的诱导分化及其功能有明显的抑制作用,这可能是肿瘤细胞逃避机体免疫监视的机制之一。
Abstract:
To study the influence of microenvironment created by dissoluble cytokines derived from highly metastatic colon carcinoma cell SW620 on the differentiation and function of human dendritic cell (DC) from peripheral blood monouclear cell (PBMC),and to provide the rationale for the clinical application of DC vaccine.Methods:PBMC was isolated by density gradient centrifugation and cultured with rhGMCSF, rhIL4. The tumour conditioned medium of SW620 cell was added on day 2 and the medium was half changed every other day.Antigen of SW620 was added on day 4 and lipopolysaccharide (LPS) was added on day 6.The DC and tumourassociated dendritic cell(TADC) were collected on day 8 for further study. The cells appearance, immunophenotype, CD1a mRNA, mixed lymphocyte reaction and CTL effects were detected.Results:The appearance of TADC was inhibited.There were significant differences on the positive rates of CD86,CD1a among PBMC,DC and TADC (F was 46.95,19.09,P<0.001). Compared to DC,in TADC, the positive rates of CD86 decreased from (68.56±8.04)% to (42.41±10.87)%, CD1a from (55.71±12.12)% to (26.60±12.03)%,respectively (P<0.05),the CD1a gene expression weakened. The proliferation[(112.53±7.16)% vs. (91.26±6.62)%] and killing[(62.42±0.57)% vs.(50.37±2.21)%] capacity of T cells activated by TADC was lower than those of DC (t was 6.17,17.41,P<0.001).Conclusion:The tumour microenvionment stimulated by the tumour conditioned medium of SW620 cell has inhibitory effect on differentiation and function of DC, which may be one of the mechanisms on tumor immune escape.

参考文献/References:

[1]Lipscomb MF,Masten BJ.Dendritic cells:immune regulators in health and disease[J].Physiol Rev,2002,82(1):97
[2]Casas R,Skarsvik S,Lindstrm A,et al.Impaired maturation of monocytederived dendritic cells from birch allergic individuals in association with birchspecific immune responses[J].Scand J Immunol,2007,66(5):591
[3]Smyth MJ,Godfrey DI,Trapani JA.A fresh look at tumor immunosurveillance and immunotherapy[J].Nat Immunol,2001,2(4):293
[4]买玲,杨洪艳,张义国,等.肿瘤抗原脉冲致敏的小鼠树突状细胞疫苗的制备及抗肿瘤作用的实验研究[J].中华消化杂志,2000,20(4):285
[5]张书峰,蔡婷,马长路,等.血源性树突状细胞融合疫苗抗恶性黑色素瘤的应用研究[J].中国医刊,2004,39(5):35
[6]He XZ,Wang L,Zhang YY.An effective vaccine against colon cancer in mice:use of recombinant adenovirus interleukin12 transduced dendritic cells[J].World J Gastroenterol,2008,14(4):532
[7]路静,赵军,宋谦, 等.人B72瘤苗与DC瘤苗体外联合诱导抗食管癌的作用[J].世界华人消化杂志,2005,13(12):1 382
[8]Ai LM,Ren HY,Shi YJ.Human/Mouse chimeric antiCD20 monoclonal antibody enhances antigen presentation in dendritic cells and induces antilymphoma CTL effects[J].Zhongguo Shi Yan Xue Ye Xue Za Zhi,2007,15(6):1 247
[9]Eichler H,Nguyen XD,Roelen D,et al.Multicenter study on in vitro characterization of dendritic cells[J].Cytotherapy,2008,10(1):21
[10]Kim R,Emi M,Tanabe K.Functional roles of immature dendritic cells in impaired immunity of solid tumour and their targeted strategies for provoking tumour immunity[J].Clin Exp Immunol,2006,146(2):189
[11]Ghiringhelli F,Puig PE,Roux S,et al.Tumor cells convert immature myeloid dendritic cells into TGFbetasecreting cells inducing CD4+CD25+ regulatory T cell proliferation[J].J Exp Med,2005,202(7):919
[12]Boussiotis VA,Freeman GJ,Gray G,et al.B7 but not intercellular adhesion molecule1 costimulation prevents the induction of human alloantigenspecific tolerance[J].J Exp Med,1993,178(5):1 753

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备注/Memo

备注/Memo:
*河南省卫生厅科技攻关基金资助项目20060011 #通讯作者,男,1954年生,博士,教授,研究方向:肿瘤生物治疗,Email:dongzm@zzu.edu.cn
更新日期/Last Update: 2010-05-14