小鼠乳腺癌干细胞免疫相关分子表达和免疫浸润的分析

doi:10.16352/j.issn.1001-6325.2022.06.002

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (6): 876-882.doi: 10.16352/j.issn.1001-6325.2022.06.002

小鼠乳腺癌干细胞免疫相关分子表达和免疫浸润的分析

李昱阳, 李钊璇, 罗云萍, 陈翀^*

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

收稿日期:2021-04-26 修回日期:2022-01-07 出版日期:2022-06-05 发布日期:2022-06-02
通讯作者: * chenchong86@ibms.pumc.edu.cn
基金资助:
国家自然科学基金(81972795);国际合作项目(2018YFE0114300)

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

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

Received:2021-04-26 Revised:2022-01-07 Online:2022-06-05 Published:2022-06-02
Contact: * chenchong86@ibms.pumc.edu.cn

摘要/Abstract

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。

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

Abstract: 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.

Key words: cancer stem cells, immune checkpoint, antigen presentation, tumor immune evasion, tumor immune infiltration

中图分类号:

R392.9

李昱阳, 李钊璇, 罗云萍, 陈翀. 小鼠乳腺癌干细胞免疫相关分子表达和免疫浸润的分析[J]. 基础医学与临床, 2022, 42(6): 876-882.

LI Yu-yang, LI Zhao-xuan, LUO Yun-ping, CHEN Chong. Analysis of the immune-related molecule expression and immune infiltration in mouse breast cancer stem cells[J]. Basic & Clinical Medicine, 2022, 42(6): 876-882.

参考文献

[1] Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells[J]. Nature, 2001, 414: 105-111.
[2] Brown HK, Tellez-Gabriel M, Heymann D. Cancer stem cells in osteosarcoma[J]. Cancer Lett, 2017, 386: 189-195.
[3] Castelli G, Pelosi E, Testa U. Liver cancer: molecular characterization, clonal evolution and cancer stem cells[J]. Cancers (Basel), 2017, 9:127.doi:10.3390/cancers9090127.
[4] Markowska A, Sajdak S, Huczyński A, et al. Ovarian cancer stem cells: a target for oncological therapy[J]. Adv Clin Exp Med, 2018, 27: 1017-1020.
[5] Sancho P, Barneda D, Heeschen C. Hallmarks of cancer stem cell metabolism[J]. Br J Cancer, 2016, 114: 1305-1312.
[6] Yan Y, Zuo X, Wei D. Concise review: emerging role of CD44 in cancer stem cells: a promising biomarker and therapeutic target[J]. Stem Cells Transl Med, 2015, 4: 1033-1043.
[7] Pajonk F, Vlashi E, McBride WH. Radiation resistance of cancer stem cells: the 4 R's of radiobiology revisited[J]. Stem Cells, 2010, 28: 639-648.
[8] Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment[J]. Nat Immunol, 2013, 14: 1014-1022.
[9] Shen H, Sun T, Hoang HH, et al. Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells[J]. Semin Immunol, 2017, 34: 114-122.
[10] Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer[J]. J Immunother Cancer, 2016, 4: 59.doi:10.1186/s40425-016-0165-6.
[11] Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade[J]. Science, 2018, 359: 1350-1355.
[12] de Miguel M, Calvo E. Clinical challenges of immune checkpoint inhibitors[J]. Cancer Cell, 2020, 38: 326-333.
[13] 白丽鹏, 陈翀, 刘妍,等.LIN28B调控miRNAs维持MCF-7肿瘤干细胞的干性特征[J]. 基础医学与临床,2015, 35: 754-760.
[14] 曹峰琦,陈翀,刘妍,等.肿瘤pH微环境通过激活β-catenin/TCF4增强人乳腺癌肿瘤细胞的干性[J]. 基础医学与临床,2014, 34: 622-627.
[15] Agudo J, Park ES, Rose SA, et al. Quiescent tissue stem cells evade immune surveillance[J]. Immunity, 2018, 48: 271-285.

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

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 10

编辑推荐

Metrics

本文评价

[1]	甘兹颖, 唐慧. 溶瘤病毒联合PD-1/PD-L1抑制剂的研究进展[J]. 基础医学与临床, 2022, 42(4): 651-655.
[2]	谢丽君, 朱高红, 赵继华, 张海波, 王娇. 甲状腺癌肿瘤干细胞的来源和存活途径[J]. 基础医学与临床, 2022, 42(2): 321-324.
[3]	尹婕, 潘凌亚, 温仪萍, 黄虹, 曾靖, 李晓莹, 韩甜甜, 金滢, 李艳. 人上皮性卵巢癌细胞系侧群细胞的肿瘤干细胞样细胞生物学特性及膜蛋白差异表达的鉴定[J]. 基础医学与临床, 2022, 42(2): 221-227.
[4]	张若曦韩冰. 免疫检查点抑制剂治疗骨髓增生异常综合征的研究进展[J]. 基础医学与临床, 2021, 41(8): 1210-1215.
[5]	董保龙韩彩文史明郑文学杨晓军. 波形蛋白在肝细胞癌中的研究进展[J]. 基础医学与临床, 2020, 40(2): 238-242.
[6]	张晨郭建赫慧文王胜男陈惠琳段昭君罗云萍. M2型巨噬细胞来源外泌体对乳腺癌细胞系4T1干性特征的影响[J]. 基础医学与临床, 2019, 39(6): 798-804.
[7]	徐小涛吉婷婷. microRNA与肿瘤及肿瘤干细胞的研究进展[J]. 基础医学与临床, 2018, 38(9): 1361-1365.
[8]	孙宇孙宁杨绍时宋国栋. 肿瘤干细胞作为胰腺癌治疗潜在靶点的研究进展 [J]. 基础医学与临床, 2014, 34(7): 1006-1009.
[9]	敖宁刘玉琴. USP22在肿瘤发生发展中的作用研究进展[J]. 基础医学与临床, 2012, 32(10): 1235-1238.
[10]	韩兴文王栓科康学文. 肿瘤干细胞与骨肉瘤[J]. 基础医学与临床, 2009, 29(6): 654-656.