YTHDF2 inhibition potentiates radiotherapy antitumor efficacy
文献类型：期刊论文
| 作者 | Wang, Liangliang1,2; Dou, Xiaoyang3,4,5; Chen, Shijie6; Yu, Xianbin3,4,5; Huang, Xiaona1,2; Zhang, Linda3,4,5; Chen, Yantao6; Wang, Jiaai1,2; Yang, Kaiting1,2; Bugno, Jason1,2,7 |
| 刊名 | CANCER CELL
 |
| 出版日期 | 2023-07-10 |
| 卷号 | 41期号:7页码:1294-+ |
| ISSN号 | 1535-6108 |
| DOI | 10.1016/j.ccell.2023.04.019 |
| 通讯作者 | Luo, Cheng(cluo@simm.ac.cn) ; Liang, Hua Laura(hualiang@uchicago.edu) ; He, Chuan(chuanhe@uchicago.edu) ; Weichselbaum, Ralph R.(rweichselbaum@bsd.uchicago.edu) |
| 英文摘要 | RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells aug-ments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhib-iting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-KB signaling; YTHDF2 in turn leads to NF-KB activation by directly binding and degrading transcripts encoding negative regulators of NF-KB signaling, resulting in an IR-YTHDF2-NF-KB circuit. Pharmacological inhibition of YTHDF2 over-comes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations. |
| WOS关键词 | NF-KAPPA-B ; STEREOTACTIC BODY RADIOTHERAPY ; DYNAMIC RNA MODIFICATIONS ; TUMOR MICROENVIRONMENT ; CELL DIFFERENTIATION ; SUPPRESSOR-CELLS ; GENE-EXPRESSION ; PROGNOSIS ; RADIATION ; RESPONSES |
| 资助项目 | NIH R01 grant[R01CA262508] ; NIH R01 grant[RM1HG008935] ; Chicago Tumor Institute ; Ludwig Cancer Research Foundation ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[21820102008] ; Clinical Therapeutics Training Grant[T32GM007019] ; National Cancer Institute[K12CA139160] ; German Research Foundation (Deut-sche Forschungsgemeinschaft - DFG)[455353745] |
| WOS研究方向 | Oncology ; Cell Biology |
| 语种 | 英语 |
| 出版者 | CELL PRESS |
| WOS记录号 | WOS:001039387000001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306854]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Luo, Cheng; Liang, Hua Laura; He, Chuan; Weichselbaum, Ralph R. |
| 作者单位 | 1.Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA 2.Univ Chicago, Ludwig Ctr Metastasis Res, Chicago, IL 60637 USA 3.Univ Chicago, Dept Chem, Dept Biochem & Mol Biol, Chicago, IL 60637 USA 4.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA 5.Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Univ Chicago, Comm Clin Pharmacol & Pharmacogen, Chicago, IL USA 8.Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Jinan 250117, Peoples R China 9.Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, D-20246 Hamburg, Germany 10.Chinese Acad Agr Sci, Inst Anim Sci, State Key Lab Anim Nutr, Beijing 100193, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Liangliang,Dou, Xiaoyang,Chen, Shijie,et al. YTHDF2 inhibition potentiates radiotherapy antitumor efficacy[J]. CANCER CELL,2023,41(7):1294-+. |
| APA | Wang, Liangliang.,Dou, Xiaoyang.,Chen, Shijie.,Yu, Xianbin.,Huang, Xiaona.,...&Weichselbaum, Ralph R..(2023).YTHDF2 inhibition potentiates radiotherapy antitumor efficacy.CANCER CELL,41(7),1294-+. |
| MLA | Wang, Liangliang,et al."YTHDF2 inhibition potentiates radiotherapy antitumor efficacy".CANCER CELL 41.7(2023):1294-+. |
入库方式： OAI收割
来源：上海药物研究所
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