结直肠肿瘤组织中LAPP^＋CD4^＋ T淋巴细胞的表型特征  

Phenotypic characteristics of LAP^＋CD4^＋ T lymphocytes in colorectal cancer tissues

作　　者：钟武[1] 江志远[2] 钟世彪[2] 张磊昌[2] 黄家豪[2] 张森[2] 陈利生[2] 曹云飞[2] 

机构地区：[1]南昌大学附属赣州医院胃肠外科,341000 [2]广西医科大学第一附属医院结直肠肛门外科,南宁530021

出　　处：《中华肿瘤杂志》2016年第8期596-601,共6页Chinese Journal of Oncology

基　　金：国家自然科学基金(81260316)；2014年广西研究生教育创新计划资助项目( YCBZ2014032)Fund programsNational Natural Science Foundation of China (81260316)；The Graduate Creativity Education Project of Guangxi Autonomous Region

摘　　要：目的 分析结直肠癌患者外周血及肿瘤组织中LAP^＋CD4^＋ T淋巴细胞表型特征，及其在结直肠癌肿瘤微环境中促瘤作用的相关分子机制。方法 选取2014年1月至2014年5月间初次手术治疗的50例结直肠癌患者外周血、肿瘤组织和相应正常组织，以25例健康志愿者外周血为对照组，流式细胞术分析LAP^＋CD4^＋ T淋巴细胞和LAP-CD4＋ T淋巴细胞中趋化因子受体7（CCR7）、白细胞分化抗原45RA （CD45RA）、叉状头转录因子p3（Foxp3）、细胞毒T淋巴细胞相关抗原4（CTLA-4）、趋化因子受体4（CCR4）、趋化因子受体5（CCR5）的表达水平。结果 健康志愿者和结直肠癌患者外周血中LAP^＋CD4^＋ T淋巴细胞比例分别为（1.49±1.00）%和（9.44±3.18）%，差异有统计学意义（P〈0.001）。结直肠癌组织和相应正常组织中LAP^＋CD4^＋ T淋巴细胞比例分别为（11.76±3.74）%和（3.87±1.64）%，差异有统计学意义（P〈0.001）。健康志愿者和结直肠癌患者外周血和相应正常组织中的LAP^＋CD4^＋ T淋巴细胞主要为中央记忆T淋巴细胞，而结直肠癌组织中的LAP^＋CD4^＋ T淋巴细胞主要为效应记忆T淋巴细胞。结直肠癌组织中，LAP^＋CD4^＋ T淋巴细胞和LAP-CD4＋ T淋巴细胞中Foxp3表达水平分别为（3.87±1.12）%和（16.70±2.61）%，CTLA-4表达水平分别为（36.36±19.14） %和（19.60±8.91） %，CCR4表达水平分别为（37.72±11.14 ）和（30.06±9.14）%，CCR5表达水平分别为（18.86±7.10） %和（13.92±3.31）%，差异均有统计学意义（均P〈0.001）。结论 LAP^＋CD4^＋ T淋巴细胞具有更高的肿瘤富集趋势，易聚积于肿瘤微环境中。与传统的CD4＋CD25＋调节性T淋巴细胞不同，LAP^＋CD4^＋ T淋巴细胞中Foxp3低表达，CTLA-4、CCR4和CCR5高表达，具有独特的表型特征。Objective To analyze the phenotypic characteristics of LAP^＋CD4^＋ lymphocytes and investigate their molecular mechanisms in coloreetal cancer （CRC） microenvironment. Methods Fifty colorectal cancer patients treated in our two hospitals from January 2014 to May 2014 were included in this study. Their tumor tissues and adjacent normal tissues, peripheral blood samples, and peripheral blood samples of 25 healthy donors （HD） were collected to isolate the lymphocytes. The different expressions of CCRT, CD45RA, Foxp3, CTLA-4, CCR4 and CCR5 in LAP^＋CD4^＋T and LAP CD4^＋T lymphoeytes were analyzed by flow cytometry （FCM）. Results The FCM assay detected that the percentage of LAP^＋CD4^＋ cells in peripheral blood of the CRC patients were significantly higher than that of HD [ （9.44±3.18 ）% versus （1.49±1.00）%, P〈0.0011. In addition, significantly more LAP^＋CD4^＋ cells were also recruited into tumor tissue than those in the tumor-adjacent normal tissue [ （11.76±3.74） % versus （3.87± 1.64）%, P〈0.001 ]. LAP^＋ CD4^＋ T cells in the tumor-adjacent normal tissue and peripheral blood of both HDs and CRC patients mainly displayed a central memory phenotype. However, effector memory lymphocytes were predominant in the tumor tissue.In the tumor tissue, the expression of Foxp3 in the LAP^＋CD4^＋ cells was （3.87±1.12）%, significantly lower than that in the LAP-CD4^＋T cells （ 16.70±2.61）%, （P〈0.001） ; the expression of CTLA-4 in the LAP^＋CD4^＋T cells was （36.36± 19.14）%, significantly higher than the （19.60± 8.91） % in the LAP^＋CD4^＋T cells （P〈 0.001 ） ; the expression of CCR4 in the LAP^＋CD4^＋ cells was （37.72±11.14）%, significantly higher than the （30.06±9.14）% in the LAP-CD4^＋T cells （P〈0.001）; and the expression of CCR5 in the LAP^＋CD4^＋ cells was （18.86±7.10） %, significantly higher than the （13.92±3.31）% in the LAP^＋CD4^＋ T cells （P〈0.001）. Conclusions LAP^＋CD4^＋T cells with low ex

关 键 词：结直肠肿瘤 T淋巴细胞 调节性 LAP^+CD4^+T淋巴细胞 叉状头转录因子p3 

分 类 号：R735.34[医药卫生—肿瘤]