B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:David_storm
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
AIM:To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment.METHODS:One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study.Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues.Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues;flow cytometry and immunofluorescence staining were used for detection of regulatory T cells.Data was analyzed with statistical software.RESULTS:Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues,localized in tumor cell membrane and cytoplasm,while weak or none expression of B7-H1 was detected in pared normal colorectal tissues.Meanwhile,CD3 positive T cells were found congregated in CRC tumor nest and stroma.Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P<0.0001) and tumor stroma (P=0.0200) of 102 cases of CRC tissues.Among the total T cells,a variable amount of regulatory T cells with a clear Foxp3+ (forkhead box P3) staining could be detected in CRC tissues and patients’ blood.Interestingly,in the 33 samples (15 cases of B7-H1 high CRC tissues and 18 cases of B7H1 low CRC tissues) of freshly isolated mononuclear cells from CRC tissues,the percentages of CD4+ Foxp3+ and CD8+ Foxp3+ regulatory T cells were found remarkably higher in B7-H1 high CRC tissues than in B7-H1 low CRC tissues (P=0.0024,P=0.0182),indicating that B7-H1 expression was involved in proliferation of regulatory T cell.No significant difference was found in CRC peripheral blood (P=0.0863,P=0.0678).PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell,which is expressed by activated T cell.Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells (CD4+ Foxp3/CD8+ Foxp3),which was thought to contribute to the anti-tumor immune response,highly expressed PD-1;while regulatory T cells (CD4+ Foxp3+/CD8+ Foxp3) almost failed to express PD-1.The average percentage of PD-1 expression on regulatory T cells was significantly higher than the percentage of PD-1 on conventional T cells (CD4+ Foxp3 T cell,P<0.0001;CD8+ Foxp3 T cell,P<0.0001).The diverse expression of PD-1 might lead to different fate of T cell subsets in B7-H1 over-expression CRC tumor microenvironment.CONCLUSION:B7-H1 expression in tumor cells can in hibit the conventional T cell proliferation in tumor micro environment through the PD-1 expression on conventiona T cells. AIM: To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. METHODS: One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software .RESULTS: Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor and stroma. Statistical analysis showed that B7-H1 expression level was negatively correlated to the total T cell density i Of the 102 cases of CRC tissues. Patients who received T cells in a variable amount of regulatory T cells with a clear Foxp3 + (forkhead box P3) staining could be detected in (P <0.0001) CRC tissues and patients’ blood.Interestingly, in the 33 samples (15 cases of B7-H1 high CRC tissues and 18 cases of B7H1 low CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percent of CD4 + Foxp3 + and CD8 + Foxp3 + regulatory T cells were remarkably higher in B7-H1 high CRC tissues than in B7-H1 low CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was PD-1 expression was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway carry inhibitory signal to T cell, which is expressed by activated T cell. on T cells in CRC tissues showed that conventional T cells (CD4 + Foxp3 / CD8 + Foxp3), which was thought to contribute to the anti-tumor immune response, highly expressed PD-1; while regulatory T cells (CD4 + Foxp3 + / CD8 + Foxp3) higher than the percentage of PD-1 on conventional T cells. The diverse expression of PD-1 might lead to different fates of T cell subsets in B7 (P <0.05; CD8 + Foxp3 T cell, -H1 over-expression CRC tumor microenvironment. CONCLUSION: B7-H1 expression in tumor cells can in hibit the conventional T cell proliferation in tumor micro environment through the PD-1 expression on conventions T cells.
其他文献
期待已久的春节大假即将到来,各位可能早就计划好了,有想好好吃的,有想过过瘾的,还有想跟小伙伴好好聚聚诉说一番衷肠的.但是做什么都应该有度,如果过度,功能再强大的胃也会
期刊
“八五”期间,江门航运公司抓机遇、上项目,练内功、创效益,取得了可喜成绩:一是基础建设大大加强,港口通过能力有了较大提高。“八五”期间,外贸货物吞吐量达267万余吨,年
黄格胜于1998年走马上任广西艺术学院院长职位,成为广西高校中惟一非中共党员的院长。4年多来,他以高度的历史责任感,励精图治,凝聚人心,使学院面貌发生了深刻的变化。造型
《医賸》为日本著名考据学家丹波元简所撰的一部医学笔记,汇聚了其十余年的读书心得.现从《医賸》的著书背景、命名、刊印、主要内容、考据方法以及学术价值等方面加以论述,
卡林型金矿因1962年首先在美国内华达州卡林(Carlin)地区发现故命名为卡林型金矿。与其他类型金矿床相比,卡林型金矿有其独特之处:围岩主要为不纯碳酸盐岩或其他细碎屑岩;常
会议
身兼电台主持人的孟庭苇,在主持节目中收到一位听众朋友的来信,告诉她这样一个真实的故事:一天晚上,在林目长庚医院附近,一个男孩冒雨骑摩托车带女朋友在公路上飞驶,雨后的
在分析总结前人资料的基础上,运用岩石学、岩相学、岩石地球化学以及矿床学等理论研究方法,对矿区6个开采中段坑道编录,8个钻孔岩芯编录,所取样品运用德国莱卡Leica DMRXP高级显
欧洲罕见病组织于2008年2月29日发起并组织了第一届国际罕见病日,旨在提高社会公众和政府对罕见病及罕见病群体面临的问题的认知.特意选在2月29日这个四年才有一天的日子,就
期刊
NCR 公司数据仓库事业部(Teradata Division),宣布推出保险业客户关系管理解决方案(CRM)—Behavior Analysis 行为分析软件,用于分析客户保单购买、索赔行为以及客户互动行