YTHDF1 loss in dendritic cells potentiates radiation- induced antitumor immunity via STING-dependent I IFN
文献类型：期刊论文
| 作者 | Wen, Chuangyu11,12; Wang, Liangliang10; Piffko, Andras9,11,12; Chen, Dapeng12; Yu, Xianbin6,7,8; Zawieracz, Katarzyna5; Bugno, Jason11,12; Yang, Kaiting11,12; Naccasha, Emile Z.11,12; Ji, Fei11,12 |
| 刊名 | JOURNAL OF CLINICAL INVESTIGATION
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| 出版日期 | 2024-12-02 |
| 卷号 | 134期号:23页码:14 |
| ISSN号 | 0021-9738 |
| DOI | 10.1172/JCI181612 |
| 通讯作者 | He, Chuan(chuanhe@uchicago.edu) ; Weichselbaum, Ralph R.(hualiang@uchicago.edu) |
| 英文摘要 | The RNA N 6-methyladenosine (m6A) readerYTHDF1 is implicated in cancer etiology and progression. We discovered that radiotherapy (RT) increased YTHDF1 expression in dendritic cells (DCs) of PBMCs from patients with cancer, but not in other immune cells tested. Elevated YTHDF1 expression in DCs was associated with poor outcomes for patients receiving RT. We found that loss of Ythdf1 in DCs enhanced the antitumor effects of ionizing radiation (IR) by increasing the cross-priming capacity of DCs across multiple murine cancer models. Mechanistically, IR upregulated YTHDF1 expression in DCs through stimulator of IFN genes/type I IFN (STING/IFN-I) signaling. YTHDF1 in turn triggered STING degradation by increasing lysosomal cathepsins, thereby reducing IFN-I production. We created a YTHDF1 deletion/inhibition prototype DC vaccine that significantly improved the therapeutic effect of RT and radioimmunotherapy in a murine melanoma model. Our findings reveal a layer of regulation between YTHDF1/m6A and STING in response to IR, which opens new paths for the development of YTHDF1-targeting therapies. |
| WOS关键词 | CANCER ; RADIOTHERAPY ; IMMUNOTHERAPY ; INTERFERONS ; VACCINATION ; NIVOLUMAB ; INNATE ; CD8(+) ; ROLES |
| 资助项目 | National Cancer Institute (NCI), NIH[U54CA274291] ; Chicago Tumor Institute, an endowment from the Ludwig Cancer Research Foundation ; NIH[R01CA262508] ; NIH[R01CA251150] ; Walter Benjamin scholarship by the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG])[455353745] ; National Cancer Institute[K12CA139160] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001419603000018 |
| 出版者 | AMER SOC CLINICAL INVESTIGATION INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316197]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | He, Chuan; Weichselbaum, Ralph R. |
| 作者单位 | 1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Guangdong, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Nanjing Med Univ, Womens Hosp, Nanjing Women & Childrens Healthcare Hosp, Gusu Sch,State Key Lab Reproduct Med & Offspring H, Nanjing, Jiangsu, Peoples R China 4.Northwestern Univ, Biomed Engn Program, Evanston, IL USA 5.Univ Chicago, Departmentof Pathol, Chicago, IL USA 6.Univ Chicago, Howard Hughes Med Inst, Chicago, IL USA 7.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA 8.Univ Chicago, Dept Chem, Dept Biochem & Mol Biol, Chicago, IL 60637 USA 9.Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, Hamburg, Germany 10.Chinese Acad Sci, Inst Microbiol, Lab Microbiome & Microecol Technol, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wen, Chuangyu,Wang, Liangliang,Piffko, Andras,et al. YTHDF1 loss in dendritic cells potentiates radiation- induced antitumor immunity via STING-dependent I IFN[J]. JOURNAL OF CLINICAL INVESTIGATION,2024,134(23):14. |
| APA | Wen, Chuangyu.,Wang, Liangliang.,Piffko, Andras.,Chen, Dapeng.,Yu, Xianbin.,...&Weichselbaum, Ralph R..(2024).YTHDF1 loss in dendritic cells potentiates radiation- induced antitumor immunity via STING-dependent I IFN.JOURNAL OF CLINICAL INVESTIGATION,134(23),14. |
| MLA | Wen, Chuangyu,et al."YTHDF1 loss in dendritic cells potentiates radiation- induced antitumor immunity via STING-dependent I IFN".JOURNAL OF CLINICAL INVESTIGATION 134.23(2024):14. |
入库方式： OAI收割
来源：上海药物研究所
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