小鼠乳腺癌干细胞免疫相关分子表达和免疫浸润的分析  

Analysis of the immune-related molecule expression and immune infiltration in mouse breast cancer stem cells

作　　者：李昱阳 李钊璇 罗云萍[1] 陈翀[1] LI Yu-yang;LI Zhao-xuan;LUO Yun-ping;CHEN Chong(Department of Immunology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College,Beijing 100005,China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院免疫学系,北京100005

出　　处：《基础医学与临床》2022年第6期876-882,共7页Basic and Clinical Medicine

基　　金：国家自然科学基金(81972795);国际合作项目(2018YFE0114300)。

摘　　要：目的分析小鼠乳腺癌干细胞(BCSCs)中免疫相关分子的表达和肿瘤组织中免疫细胞的浸润。方法用成球培养的方法在体外富集小鼠乳腺癌细胞系4T1和4T07的肿瘤干细胞(CSCs);用实时定量PCR检测BCSCs中免疫检查点与抗原递呈相关基因的表达;用小鼠乳腺癌原位移植瘤模型和流式细胞测量术分别检测脾脏和肿瘤组织中各类免疫细胞的比例。结果用成球培养的方法可以成功富集小鼠乳腺癌干细胞4T1和4T07;与贴壁培养的肿瘤细胞相比,小鼠BCSCs中免疫检查点和抗原递呈相关基因的表达有明显差异(P<0.05)。体内的结果表明,与贴壁肿瘤细胞来源的肿瘤组织相比,肿瘤干细胞来源的肿瘤组织中浸润更多的CD4^(+)T和CD8^(+)T细胞(P<0.05),但是CD11b^(+)F4/80^(+)的巨噬细胞浸润更少(P<0.05)。结论小鼠BCSCs中免疫检查点与抗原递呈相关基因的表达有改变,且在体内可招募更多的T细胞到肿瘤组织中去。Objective To investigate the expression of immune-related molecules and the infiltration of immune cells from mouse breast cancer stem cells(BCSCs).Methods Mouse BCSCs of 4T1 and 4T07 were enriched by spheroid culturing;the expression of immune checkpoint-and antigen presentation-associated genes in BCSCs was detected by RT-qPCR;the proportion of various types of immune cells in spleen or tumor tissue of orthotopic tumor model mouse was detected by flow cytometry.Results The mouse BCSCs 4T1 and 4T07 were successfully enriched by spheroid culturing;the expression of immune checkpoints-and antigen presentation-associated genes were significantly different as compared with the adherent cancer cells;the proportion of both CD4^(+)and CD8^(+)T cell increased.However,the proportion of macrophage(CD11b^(+)/F480^(+))was decreased in tumors formed by spheroid cells as compared with that in the tumors formed by adherent cells.Conclusions The expression of immune checkpoint-and antigen presentation-associated genes in BCSCs were significantly different and the infiltration of T cells increased in tumors formed by BCSCs.

关 键 词：肿瘤干细胞 免疫检查点 抗原递呈 肿瘤免疫逃逸 肿瘤免疫浸润 

分 类 号：R392.9[医药卫生—免疫学]