构建与评价不同免疫微环境小鼠肝癌模型  

Construction and evaluation of hepatocellular carcinoma models in mice with different immune microenvironments

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作  者:仲雨洁 戴宇阳 伏世杰 郑康炼 朱超凡 曹广[1] 徐亮 牛传鑫 樊晓雨 王晓东[1] ZHONG Yujie;DAI Yuyang;FU Shijie;ZHENG Kangian;ZHU Chaofan;CAO Guang;XU Liang;NIU Chuanzin;FAN Xiaoyu;WANG Xiaodong*(Department of Interventional Therapy,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research,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介入治疗科、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:《中国介入影像与治疗学》2025年第4期260-266,共7页Chinese Journal of Interventional Imaging and Therapy

基  金:北京市自然科学基金面上项目(7212198);国家自然科学基金面上项目(82172039);北京市医院管理中心临床医学发展专项经费资助(ZYLX202117)。

摘  要:目的构建不同肿瘤免疫微环境(TIME)小鼠肝癌模型,观察其TIME差异。方法分别以H22及hepal-6同源肝癌细胞系构建C57小鼠皮下移植瘤模型(记为H22组与hepal-6组,每组8只),评价其TIME差异,以免疫组织化学技术定量分析其中T细胞、CD4+T细胞、CD8+T细胞、调节性T细胞及B细胞浸润的差异;以流式细胞术检测外周血与肿瘤实质内免疫细胞亚群组成;基于高通量转录组测序技术解析肿瘤组织基因表达谱特征,结合基因本体论(GO)及京都基因与基因组百科数据库(KEGG)进行免疫相关信号通路富集分析。结果H22组呈冷肿瘤、hepal-6组呈热肿瘤TIME特征。H22组肿瘤组织中的T细胞、CD4+T细胞及CD8十T细胞数均少于,而外周血中的T细胞、CD4+T细胞及CD8+T细胞占比均高于hepal-6组(P均<0.05)。相比H22组,hepal-6组肿瘤组织上调基因在肿瘤免疫激活相关信号通路中显著富集。结论H22与hepal-6小鼠肝癌模型分别呈现冷、热肿瘤TIME特征,前者肿瘤组织中的免疫细胞数量显著低于后者。Objective To construct mice hepatocellular carcinoma models with different tumor immune microenvironments(TIME)and explore the differences.Methods H22 and hepal-6 were used to construct subcutaneous transplantation tumor model of C57 mice as homologous hepatocellular carcinoma cell lines(denoted as H22 group and hepal-6 group,each n=8),and the differences of TIME were evaluated,Immunohistochemistry was used to detect and quantify the infiltration of T cells,CD4+T cells,CD8+T cells,regulatory T cells and B cells in TIME.Flow cytometry was performed to detect the differences of composition of immune cell subpopulations in peripheral blood and tumor parenchyma.Gene expression profile characteristics of tumor tissue were analyzed based on high-throughput transcriptome sequencing technology,and enrichment analyses of immune-related signaling pathways were evaluated combined with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG).Results H22 group showed cold and hepal-6 group showed hot TIME characteristics.The number of T cells,CD4+T cells and CD8+T cells in tumor tissue of H22 group were all lower,while the proportion of T cells,CD4+T cells and CD8+T cells in peripheral blood were all higher than those of hepal-6 group(all P<0.05).Compared with H22 group,up-regulated genes of tumor tissue in hepal-6 group expressed significantly enriched in tumor immune activation-related signaling pathways.Conclusion H22 and hepal-6 hepatocellular carcinoma models showed distinct TIME characteristics of cold and hot tumors,respectively,and the amount of immune cells in tumor tissue of the former were significantly lower than those in the latter.

关 键 词:肝肿瘤 实验性 小鼠 肿瘤微环境 免疫疗法 动物实验 

分 类 号:R735.7[医药卫生—肿瘤] R-332[医药卫生—临床医学]

 

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