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ResearchIn-Press PreviewImmunologyOncology Open Access | 10.1172/JCI181612
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Wen, C. in: JCI | PubMed | Google Scholar
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Wang, L. in: JCI | PubMed | Google Scholar |
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Chen, D. in: JCI | PubMed | Google Scholar
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Yu, X. in: JCI | PubMed | Google Scholar |
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Yang, K. in: JCI | PubMed | Google Scholar |
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Wang, J. in: JCI | PubMed | Google Scholar
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Luo, S. in: JCI | PubMed | Google Scholar
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Tan, L. in: JCI | PubMed | Google Scholar
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Shen, B. in: JCI | PubMed | Google Scholar
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Find articles by Luo, C. in: JCI | PubMed | Google Scholar |
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, United States of America
2Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Germany
4Department of Chemistry, University of Chicago, Chicago, United States of America
5Department of Pathology, University of Chicago, Chicago, United States of America
6Biomedical Engineering Program, Northwestern University, Evanston, United States of America
7State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
8Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Published September 26, 2024 - More info
RNA N6-methyladenosine (m6A) reader YTHDF1 is implicated in cancer etiology and progression. We discovered that radiotherapy (RT) increased YTHDF1 expression in dendritic cells (DCs) of PBMCs from cancer patients, but not in other immune cells tested. Elevated YTHDF1 expression of DCs was associated with poor outcomes in patients receiving RT. We found that loss of Ythdf1 in DCs enhanced the antitumor effects of ionizing radiation (IR) via increasing the cross-priming capacity of DCs across multiple murine cancer models. Mechanistically, IR upregulated YTHDF1 expression in DCs through 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, significantly improving the therapeutic effect of RT and radio-immunotherapy in a murine melanoma model. Our findings reveal a new layer of regulation between YTHDF1/m6A and STING in response to IR, which opens new paths for the development of YTHDF1-targeting therapies.