CD47型
癌症研究
胶质瘤
干细胞
抗辐射性
肿瘤微环境
癌症干细胞
生物
辐射敏感性
放射治疗
免疫学
吞噬作用
细胞生物学
医学
细胞培养
内科学
遗传学
肿瘤细胞
作者
Ting Sun,Bin Liu,Yufei Cao,Yanyan Li,Lize Cai,Wei Yang
出处
期刊:Cancer Letters
[Elsevier]
日期:2024-02-01
卷期号:583: 216605-216605
被引量:2
标识
DOI:10.1016/j.canlet.2023.216605
摘要
Radiotherapy alters the tumor microenvironment and reprograms cellular metabolism. Transition of tumor cell phenotypes contributes to post-radiotherapy tumor recurrence. Low radiosensitivity of glioma stem cells is one of the reasons for radiotherapy failure. Here, we found that radiotherapy resulted in a higher proportion of infiltration of inflammatory macrophages in glioma non-stem cell grafts compared with that in glioma stem cell-transplanted tumors in a mouse model, where immunosuppressive macrophages dominated in the tumor microenvironment. In radioresistant glioma stem cells, ionizing radiation upregulated CD47 expression by AMP-activated protein kinase (AMPK), resulting in the inhibition of phagocytosis and the promotion of M2-like polarization in macrophages. Ionizing radiation promoted H3K4 methylation on CD47 promotor by downregulating KDM5A. Hyper-phosphorylated retinoblastoma protein RB maintained its dissociation status with KDM5A following AMPK activation, which inhibited the demethylated function of KDM5A. In contrast, in radiosensitive glioma non-stem cells, RB S807/S811 hypo-phosphorylation contributed to the binding of RB with KDM5A, which suppressed H3K4 methylation on CD47 promotor. In addition, ionizing radiation promoted H3K27 acetylation on CD47 promotor by HDAC7 in glioma stem cells. These data suggested that glioma stem cells reprogrammed the tumor immune microenvironment by epigenetic editing to escape macrophage phagocytosis after ionizing radiation. Targeting CD47 might be a potential strategy to sensitize glioblastoma to radiotherapy.
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