CD4＋CD25＋叉头框蛋白p3＋调节性T细胞在结直肠癌中抑制肿瘤免疫的机制  

Mechnism of CD4＋ CD25＋ forkhead box P3 ＋regulatory T cells suppressing the tumor immunity in colorectal cancer

作　　者：朱晓文[1] 王欣[3] 朱尤庆[1] 陈志芬[1] 兰海 吴洲清 陈家宽 

机构地区：[1]武汉大学中南医院消化内科,430071 [2]肿瘤外科肿瘤生物学行为湖北省重点实验室 [3]通城县人民医院普外科

出　　处：《中华实验外科杂志》2014年第7期1578-1581,F0004,共5页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81072152）;湖北省自然科学基金资助项目（2011CDB531）;湖北省卫生厅资助项目（2012CD201）

摘　　要：目的 探讨CD4＋CD25＋叉头框蛋白p3（Foxp3）-＋调节性T细胞在结直肠癌中抑制肿瘤免疫的机制。方法收集结直肠癌组织48例,息肉组织22例,正常组织21例,采用免疫组织化学法检测Foxp3-＋调节性T细胞及白细胞介素（IL）-10阳性肿瘤细胞在上述组织中的含量,逆转录-聚合酶链反应（RT-PCR）法检测Foxp3及信号转导与转录激活因子（STAT3）mRNA在不同组织中的基因表达,同时采用x2检验分析上述指标与肿瘤临床病理特征之间的关系。结果 Foxp3及IL-10在结直肠癌组织中阳性细胞表达率分别为45.8%和68.8%,较息肉组织（13.6%和31.8%）及正常组织（9.5%和23.8%）显著升高（P〈0.01）,肿瘤组织中Foxp3及STAT3 mRNA的相对表达量分别为0.644±0.059、0.343±0.036,较息肉组织（0.322±0.020、0.212±0.028）及正常组织（0.309±0.016、0.202±0.021）明显升高（P〈0.01）,结直肠癌组织中Foxp3与STAT3基因表达量呈正相关（r=0.526,P〈0.05）,Foxp3与IL-10蛋白表达呈正相关（r=0.314,P〈0.05）,肿瘤组织中Foxp3的表达量与组织学分级、淋巴结转移、TNM分期明显相关（P〈0.05）,与年龄、性别无明显相关（P〈0.05）。结论 CD4＋CD25＋Foxp3＋调节性T细胞通过Foxp3及其他相关抑制性细胞因子的表达抑制肿瘤免疫,进而引起肿瘤免疫逃逸,从而促进肿瘤的发生发展。Objective To study the mechanism of CD4 ± CD25 ± forkhead box P3 （Foxp3） ± regu- latory T ceils inhibiting the tumor immunity in colorectal cancer. Methods Thirty-two cases of colorectal carcinoma, 21 cases of polypus, and 18 cases of normal tissues were collected. T he immunohistochemistry was used to measure the number of Foxp3 ± regulatory T cells and interleukin （IL） -10 positive cells in above tissues, and reverse transcription-polymerase chain reaction （RT-PCR） was done to dectect the ex pression of Foxp3 and signal transducers and activators of transcription 3 （ STAT3 ） mRNA in different tissues. The relationship between the above indexes and elinicopathological features was analyzed. Results The expression rate of positive cells of Foxp3 and IL-10 in coloreetal cancer was respectively 45.8% and 68.8%, significantly higher than in the polypus tissues （13.6% and 1.8% ） and normal tissues （9.5% and 23.8% ） （P 〈0. 01 for all）. The relative expression amount of Foxp3 and STAT3 mRNA in tumor tissue was respectively 0. 644 ± 0. 059 and 0. 343 ± 0. 036, which was significantly increased as compared with polypus （0. 322 ±0. 020 and 0. 212 ±0. 028） and normal tissue （0. 309 ±0. 016 and 0. 202 ±0. 021 ） （P 〈 0. 01 for all）. The Foxp3 mRNA expression in colorectal cancer tissues was positively correlated with STAT3 （r = 0. 526. P 〈 0. 05 ）. The Foxp3 protein expression wass positively correlated with IL-10 （ r = 0. 314,P 〈 0. 05）. The expression of Foxp3 in cancer patients was visihley correlated with the histological grade, lymph node metastasis and TNM stage （ P 〈 0.05 ）, and there was no visible correlation with ageand gender （ P 〉 0. 05 ）. Conclusion CD4 ± CD25 ± Foxp3 ± regulatory T cells inhibit tumor immunity and induce tumor immune escape through the expression of Foxp3 and some other related inhibitory cytokines, and finally promote the tumor progression.

关 键 词：调节性T细胞 转录因子叉头框蛋白p3 信号转导与转录激活因子 结直肠癌 肿瘤免疫 

分 类 号：R735.37[医药卫生—肿瘤]