CD147阳性胃癌肿瘤微环境免疫特征分析  

Analysis of immune features of tumor microenvironment in CD147-positive gastric cancer

作　　者：郏科人 谢意 王雅坤[1] 章程[1] 齐长松 沈琳[1] 陈杨 Jia Keren;Xie Yi;Wang Yakun;Zhang Cheng;Qi Changsong;Shen Lin;Chen Yang(Department of Gastrointestinal Oncology,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所消化肿瘤内科恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《肿瘤综合治疗电子杂志》2023年第2期139-145,共7页Journal of Multidisciplinary Cancer Management(Electronic Version)

基　　金：国家自然科学基金青年科学基金项目(82203881);国家自然科学基金重大研究计划(91959205);北京市自然科学基金面上项目(7222021)。

摘　　要：目的通过分析肿瘤微环境中免疫细胞的表型与丰度,研究CD147阳性胃癌的临床病理特征与免疫特征。方法收集2014年7月至2019年12月于北京大学肿瘤医院消化肿瘤内科就诊的80例胃腺癌患者的肿瘤组织标本,通过多重免疫荧光原位技术检测肿瘤微环境中的16种蛋白质,采用计算机辅助图像分析技术识别丰富的细胞表型并计算各类细胞亚型的密度。在此基础上,分析CD147阳性胃癌患者免疫细胞密度与胃癌临床病理亚型的关联,比较CD147阳性与阴性胃癌肿瘤微环境中免疫细胞丰度差异。结果较高的CD147阳性细胞密度与晚期胃癌以及联合阳性评分(combined positive score,CPS)≥5相关。生存分析表明,CD147阴性胃癌组较阳性胃癌组具有更长的中位生存期(37.57个月∶24.63个月;P=0.006)。免疫细胞亚型分析表明,耗竭性CD8^(+)T细胞亚型(CD8^(+)TIM-3^(+)T细胞和CD8^(+)LAG-3^(+)T细胞)、CD4^(+)T细胞亚型(CD4^(+)CTLA-4^(+)T细胞、CD4^(+)Fox P3^(+)T细胞和CD4^(+)Fox P3^(+)CTLA-4^(+)T细胞)、巨噬细胞与中性粒细胞在CD147阳性胃癌组中具有更高的密度(均P<0.05)。结论CD147阳性胃癌患者相对CD147阴性患者预后较差。CD147阳性胃癌肿瘤微环境中富含免疫抑制性细胞成分。Objective To study the clinicopathological features of CD147-positive gastric cancer and potential mechanisms by analyzing the phenotype and abundance of cell components in the tumor microenvironment.Method The pre-treatment tumor tissue samples of 80 patients who suffered from gastric cancer and were treated in Peking University Cancer Hospital from July 2014 to December 2019 were collected.The 16 proteins in the tumor microenvironment were detected in situ by multiplex immunofluorescence.Computer-aided image analysis techniques were used to identify complex cell phenotypes and calculate the density of various cell subtypes.Then,the relationship between the density of CD147-positive cells and the clinicopathological subtypes of gastric cancer was analyzed,and the densities of immune cell subsets in the tumor microenvironment of CD147-positive and negative gastric cancer were compared.Result The higher density of CD147-positive cells was also associated with advanced gastric cancer and combined positive score(CPS)≥5.Survival analysis showed that CD147-negative gastric cancer group had a longer median survival than that in CD147-positive gastric cancer group(37.57 months vs.24.63 months;P=0.006).Immune cell subtype analysis revealed that the densities of exhausted CD8^(+)T cell subtypes(CD8^(+)TIM-3^(+)T cells and CD8^(+)LAG-3^(+)T cells),CD4^(+)T cell subtypes(CD4^(+)CTLA-4^(+)T cells,CD4^(+)FoxP3^(+)T cells,and CD4^(+)FoxP3^(+)CTLA-4^(+)T cells),macrophages and neutrophils were higher in CD147-positive gastric cancer group than those in CD147-negative gastric cancer group(all P<0.05).Conclusion CD147-positive gastric cancer patients have inferior survival compared with CD147-negative gastric cancer patients.CD147-positive gastric cancer harbors an immunosuppressive tumor microenvironment.

关 键 词：胃癌 CD147 肿瘤微环境 预后 

分 类 号：R735.2[医药卫生—肿瘤]