Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells
文献类型：期刊论文
| 作者 | Fan, Dandan1; Yue, Qi2,3; Chen, Jian1; Wang, Cong1; Yu, Ruilin4; Jin, Ziyi1; Yin, Shujie1; Wang, Qinyue5; Chen, Luo1; Liao, Xueling1 |
| 刊名 | ONCOIMMUNOLOGY
 |
| 出版日期 | 2021 |
| 卷号 | 10期号:1页码:13 |
| ISSN号 | 2162-402X |
| 关键词 | Wnt/beta-catenin IDH1-wildtype glioblastoma Microglia Phenotypic polarization |
| DOI | 10.1080/2162402X.2021.1932061 |
| 通讯作者 | Huang, Ruimin(rmhuang@simm.ac.cn) ; Chen, Liang(chenlianghs@126.com) |
| 英文摘要 | The vast majority (>90%) of glioblastoma (GBM) patients belong to the isocitrate dehydrogenase 1 wild type (IDH1(WT)) group which exhibits a poor prognosis with a median survival of less than 15 months. This study demonstrated numerous immunosuppressive genes as well as beta-catenin gene, pivotal for Wnt/beta-catenin signaling, were upregulated in 206 IDH1(WT) glioma patients using the Chinese Glioma Genome Atlas (CGGA) database. The increase in microglia with an immunosuppressive phenotype and the overexpression of beta-catenin protein were further verified in IDH1(WT) GBM patients and IDH1(WT) GL261 glioma allografts. Subsequently, we found that IDH1(WT) GL261 cell-derived conditioned medium activated Wnt/beta-catenin signaling in primary microglia and triggered their transition to an immunosuppressive phenotype. Blocking Wnt/beta-catenin signaling not only attenuated microglial polarization to the immunosuppressive subtype but also reactivated immune responses in IDH1(WT) GBM allografts by simultaneously enhancing cytotoxic CD8(+) T cell infiltration and downregulating regulatory T cells. Positron emission tomography imaging demonstrated enhanced proinflammatory activities in IDH1(WT) GBM allografts after the blockade of Wnt signaling. Finally, gavage administration of a Wnt signaling inhibitor significantly restrained tumor proliferation and improved the survival of model mice bearing IDH1(WT) GBM allografts. Depletion of CD8(+) T cells remarkably abrogated the therapeutic efficacy induced by the Wnt signaling inhibitor. Overall, the present work indicates that the crosstalk between IDH1(WT) glioma cells and immunosuppressive microglia is important in maintaining the immunosuppressive glioma microenvironment. Blocking Wnt/beta-catenin signaling is a promising complement for IDH1(WT) GBM treatment by improving the hostile immunosuppressive microenvironment. |
| WOS关键词 | TUMOR-ASSOCIATED MACROPHAGES ; CENTRAL-NERVOUS-SYSTEM ; REGULATORY T-CELLS ; TRANSLOCATOR PROTEIN ; GLIOMA ; GROWTH ; INHIBITION ; EXPRESSION ; SURVIVAL ; BRAIN |
| 资助项目 | Program of Shanghai Science and Technology Committee[19431900400] ; Program of Shanghai Science and Technology Committee[18441900600] ; Program of Shanghai Science and Technology Committee[20S11901400] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX01] ; National Natural Science Foundation of China[81771890] ; National Natural Science Foundation of China[91859106] ; National Natural Science Foundation of China[81771895] ; National Key R&D Programs of China [NKPs][2018YFE0118800] ; National Science Foundation for Distinguished Young Scholars of China[22025019] ; Shanghai Hospital Development Center[SHDC2020CR3073B] ; One Hundred Talent Program of Chinese Academy of Sciences |
| WOS研究方向 | Oncology ; Immunology |
| 语种 | 英语 |
| 出版者 | TAYLOR & FRANCIS INC |
| WOS记录号 | WOS:000658148100001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296991]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, Ruimin; Chen, Liang |
| 作者单位 | 1.Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai, Peoples R China 2.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Neurosurg, Shanghai, Peoples R China 3.Fudan Univ, Shanghai Med Coll, MOE Frontiers Ctr Brain Sci, Shanghai, Peoples R China 4.Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA 5.Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, Shanghai, Peoples R China 7.Fudan Univ, Dept Nucl Med, Shanghai Canc Ctr, Shanghai, Peoples R China 8.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China 9.Tianqiao & Chrissy Chen Inst Translat Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fan, Dandan,Yue, Qi,Chen, Jian,et al. Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells[J]. ONCOIMMUNOLOGY,2021,10(1):13. |
| APA | Fan, Dandan.,Yue, Qi.,Chen, Jian.,Wang, Cong.,Yu, Ruilin.,...&Li, Cong.(2021).Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells.ONCOIMMUNOLOGY,10(1),13. |
| MLA | Fan, Dandan,et al."Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells".ONCOIMMUNOLOGY 10.1(2021):13. |
入库方式： OAI收割
来源：上海药物研究所
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