食管癌组织驻留CD8^(+)T细胞分布特征及其对患者预后的影响  

Distribution features of resident CD8+T cells in human esophageal cancer tissues and its effects on the prognosis

作　　者：陈陆俊[1] 徐斌[1] 刘颖婷 李安 吴悦 葛俊伟 李迪 郑晓[1] Chen Lujun;Xu Bin;Liu Yingting;Li An;Wu Yue;Ge Junwei;Li Di;Zheng Xiao(Center of Tumor Biological Treatment,the Third Affiliated Hospital of Soochow University,Changzhou 213003,China;Shanghai Outdo Biotechnology Co.,Ltd,Shanghai 200125,China)

机构地区：[1]苏州大学附属第三医院肿瘤生物诊疗中心,常州213003 [2]上海芯超生物芯片有限公司,上海200125

出　　处：《中华消化杂志》2023年第2期89-95,共7页Chinese Journal of Digestion

基　　金：国家自然科学基金(82172689、81902386);江苏省自然科学基金(BK20211065);中国博士后科学基金面上项目(2021M700543、2021M700547);江苏省卫生健康委员会高层次卫生人才"六个一工程"拔尖人才项目(LGY2020034);常州市国际合作项目(CZ20210035)。

摘　　要：目的探讨组织驻留CD8+T(CD103+CD8+T)细胞在食管癌组织中的浸润分布特征及其临床意义。方法检索癌症基因组图谱数据库数据,分析食管癌组织中CD103+CD8+T细胞与经典1型树突状细胞(cDC1)、经典2型树突状细胞(cDC2)、3型树突状细胞(DC3)浸润程度的关系。通过上海芯超生物芯片有限公司收集于2006年1月至2008年12月手术治疗的78例食管癌患者的78份食管癌组织和75份癌旁组织的组织标本,通过电话随访患者临床资料,随访时间截至2015年7月。采用多标记免疫荧光染色和多光谱组织成像检测癌组织和癌旁组织中的CD8+T细胞、CD103+CD8+T细胞的浸润分布。比较食管癌组织与癌旁组织中CD8+T细胞、CD103+CD8+T细胞浸润数量,以及CD103+CD8+T细胞与CD8+T细胞比值百分数(以下简称为CD103+CD8+T/CD8+T)的差异。通过R语言"survminer"程序包绘制CD8+T细胞、CD103+CD8+T细胞不同程度组织浸润患者的Kaplan-Meier生存曲线,获得最佳临界值。分别比较CD8+T细胞、CD103+CD8+T细胞高度浸润与低度浸润患者的TNM分期、病理分期等临床参数。应用Wilcoxon秩和检验、卡方检验、log-rank检验和Cox比例风险回归模型评估上述指标的预后价值,相关性分析采用Spearman等级相关分析。结果食管癌患者肿瘤组织中CD103+CD8+T细胞浸润程度与cDC1、cDC2、DC3浸润程度均呈正相关(r=0.67、0.53、0.47,均P<0.001)。食管癌组织中CD8+T细胞浸润率高于癌旁组织[63.09%(42.14%,76.21%)比2.56%(1.68%,5.38%)],食管癌组织中CD103+CD8+T细胞浸润率高于癌旁组织[7.92%(1.60%,20.61%)比0.04%(0.01%,0.10%)],差异均有统计学意义(U=41.00、857.50,均P<0.001)。病理分期为Ⅰ+Ⅱ期的食管癌患者肿瘤组织中CD8+T细胞高度浸润者占比低于Ⅲ+Ⅳ期患者[57.9%(33/57)比85.7%(18/21)],TNM分期Ⅰ+Ⅱ期食管癌患者肿瘤组织中CD103+CD8+T/CD8+T高值患者占比低于Ⅲ+Ⅳ期患者[21.6%(8/37)比48.8%(20/41)],差异均有统计学意义(χObjective To explore the distribution features of resident CD8+T cells infiltration in human esophageal cancer tissues and its clinical significance.Methods Data from the Cancer Genome Atlas database were retrieved,the correlation between CD103+CD8+T cells and infiltration degree of conventional type 1 dendritic cell(cDC1),conventional type 2 dendritic cell(cDC2),type 3 dendritic cell(DC3)was investigated.From January 2006 to December 2008,78 esophageal cancer tissues and 75 adjacent normal tissues from 78 esophageal cancer patients were collected by Shanghai Outdo Biotechnology Co.,Ltd,the clinical data of patients was followed up by telephone until July 2015.The distribution of CD8+T cells and CD103+CD8+T cells in cancer tissues and adjacent normal tissues was detected by multi-color labeling techniques and multispectral tissue imaging.The differences of the number and the ratio of CD8+T cells and CD103+CD8+T cells in cancer tissues and adjacent normal tissues were compared.The Kaplan-Meier survival curves of patients with tissue infiltration of CD8+T cells and CD103+CD8+T cells at different levels were drawn through the R language"survminer"package,and the best cut-off value was obtained.TNM stage,pathological stage and other clinical parameters of patients with high and low infiltration of CD8+T cells,CD103+CD8+T cells were compared.Wilcoxon rank sum test,chi-square test,log-rank test and Cox proportional risk regression model statistical analysis were used to evaluate the prognostic value of the above indicators.Spearman correlation analysis was used for correlation analysis.Results In the cancer tissues of patients with esophageal cancer,the infiltration degree of CD103+CD8+T cells was positively correlated with the infiltration degree of cDC1 cells,cDC2 cells and DC3 cells(r=0.67,0.53 and 0.47,all P<0.001).The percentage of CD8+T cells in all cells in the whole tissue core of tumor tissues(63.09%(42.14%,76.21%))was higher than that of adjacent normal tissues(2.56%(1.68%,5.38%)),and the difference was stati

关 键 词：食管肿瘤 癌 鳞状细胞 组织驻留CD8+T细胞 预后 免疫荧光标记 免疫组织化学 

分 类 号：R735.1[医药卫生—肿瘤]