YTHDF1 loss in dendritic cells potentiates radiation-induced antitumor immunity via STING-dependent type I IFN production
The 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 patients with cancer, but not in other immune cells tested. Elevated YTHDF1 expression in DCs was a...
Gespeichert in:
| Veröffentlicht in: | The Journal of clinical investigation 2024-12, Vol.134 (23), p.1-13 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 13 |
|---|---|
| container_issue | 23 |
| container_start_page | 1 |
| container_title | The Journal of clinical investigation |
| container_volume | 134 |
| creator | Wen, Chuangyu Wang, Liangliang Piffkó, András Chen, Dapeng Yu, Xianbin Zawieracz, Katarzyna Bugno, Jason Yang, Kaiting Naccasha, Emile Z Ji, Fei Wang, Jiaai Huang, Xiaona Luo, Stephen Y Tan, Lei Shen, Bin Luo, Cheng McNerney, Megan E Chmura, Steven J Arina, Ainhoa Pitroda, Sean He, Chuan Liang, Hua Laura Weichselbaum, Ralph R |
| description | The 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 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. |
| doi_str_mv | 10.1172/JCI181612 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11601937</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A820589113</galeid><sourcerecordid>A820589113</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4132-4bd5b041b8dfd37dec335b1afcc1cd6a527383dd571c5c82c8b08ba2cdd3d8eb3</originalsourceid><addsrcrecordid>eNqNklFv0zAQxyMEYmPwwBdAlpAQPGT4Yqdxn9BU1i1o2iRWkHiyHNtpPSV2sJ1p_fa4YpQW9QH5wSff7_4--_5Z9hrwKUBVfPwyq4HBBIon2TGUJctZQdjTnfgoexHCHcZAaUmfZ0dkSoqypNVxtv6xuPw8B9S5EJCxSGmrvIlGIqm7LqDBRW2jEVEH5IVKgXE2N1aNUiskUiqOvfPI9P1oTVyjeyPQ7aK-vsiVHpJYqkZxPWhUo3p-jQbvUulG5GX2rBVd0K8e95Ps2_x8MbvMr24u6tnZVS4pkCKnjSobTKFhqlWkUloSUjYgWilBqokoi4owolRZgSwlKyRrMGtEIZUiiumGnGSffusOY9NrJVNDXnR88KYXfs2dMHw_Y82KL909B5hgmJIqKbx_VPDu56hD5L0Jm-8RVrsxcAKAKcYlwwl9-w9650Zv0_sSRSmZFhOgf6ml6DQ3tnXpYrkR5WesSEJTAJKo_AC11FanLp3VrUnHe_zpAT4tpXsjDxZ82CtITNQPcSnGEHh9-_X_2Zvv--y7HXalRRdXwXXjZurhoKj0yX5et9upAOYbZ_OtsxP7ZneMW_KPlckvcAvwbA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3144392614</pqid></control><display><type>article</type><title>YTHDF1 loss in dendritic cells potentiates radiation-induced antitumor immunity via STING-dependent type I IFN production</title><source>MEDLINE</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Wen, Chuangyu ; Wang, Liangliang ; Piffkó, András ; Chen, Dapeng ; Yu, Xianbin ; Zawieracz, Katarzyna ; Bugno, Jason ; Yang, Kaiting ; Naccasha, Emile Z ; Ji, Fei ; Wang, Jiaai ; Huang, Xiaona ; Luo, Stephen Y ; Tan, Lei ; Shen, Bin ; Luo, Cheng ; McNerney, Megan E ; Chmura, Steven J ; Arina, Ainhoa ; Pitroda, Sean ; He, Chuan ; Liang, Hua Laura ; Weichselbaum, Ralph R</creator><creatorcontrib>Wen, Chuangyu ; Wang, Liangliang ; Piffkó, András ; Chen, Dapeng ; Yu, Xianbin ; Zawieracz, Katarzyna ; Bugno, Jason ; Yang, Kaiting ; Naccasha, Emile Z ; Ji, Fei ; Wang, Jiaai ; Huang, Xiaona ; Luo, Stephen Y ; Tan, Lei ; Shen, Bin ; Luo, Cheng ; McNerney, Megan E ; Chmura, Steven J ; Arina, Ainhoa ; Pitroda, Sean ; He, Chuan ; Liang, Hua Laura ; Weichselbaum, Ralph R</creatorcontrib><description>The 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 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.</description><identifier>ISSN: 1558-8238</identifier><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI181612</identifier><identifier>PMID: 39325547</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Animal models ; Animals ; Antigen presentation ; Antitumor activity ; Cancer therapies ; Care and treatment ; Cathepsins ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Female ; Flow cytometry ; Health aspects ; Humans ; Immunotherapy ; Interferon ; Interferon Type I - genetics ; Interferon Type I - immunology ; Interferon Type I - metabolism ; Ionizing radiation ; Lymphocytes ; Melanoma ; Melanoma, Experimental - genetics ; Melanoma, Experimental - immunology ; Melanoma, Experimental - metabolism ; Melanoma, Experimental - pathology ; Melanoma, Experimental - radiotherapy ; Membrane Proteins - genetics ; Membrane Proteins - immunology ; Membrane Proteins - metabolism ; Metastasis ; Methods ; Mice ; Mice, Knockout ; Physiological aspects ; Proteins ; Radiation therapy ; Radioimmunotherapy ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - immunology ; RNA-Binding Proteins - metabolism ; Tumors ; Vaccines</subject><ispartof>The Journal of clinical investigation, 2024-12, Vol.134 (23), p.1-13</ispartof><rights>COPYRIGHT 2024 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Dec 2024</rights><rights>2024 Wen et al. 2024 Wen et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4132-4bd5b041b8dfd37dec335b1afcc1cd6a527383dd571c5c82c8b08ba2cdd3d8eb3</cites><orcidid>0000-0001-8340-5190 ; 0000-0003-3864-8382 ; 0000-0002-7508-8006 ; 0000-0001-5300-6594 ; 0000-0001-9328-5655</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601937/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601937/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39325547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wen, Chuangyu</creatorcontrib><creatorcontrib>Wang, Liangliang</creatorcontrib><creatorcontrib>Piffkó, András</creatorcontrib><creatorcontrib>Chen, Dapeng</creatorcontrib><creatorcontrib>Yu, Xianbin</creatorcontrib><creatorcontrib>Zawieracz, Katarzyna</creatorcontrib><creatorcontrib>Bugno, Jason</creatorcontrib><creatorcontrib>Yang, Kaiting</creatorcontrib><creatorcontrib>Naccasha, Emile Z</creatorcontrib><creatorcontrib>Ji, Fei</creatorcontrib><creatorcontrib>Wang, Jiaai</creatorcontrib><creatorcontrib>Huang, Xiaona</creatorcontrib><creatorcontrib>Luo, Stephen Y</creatorcontrib><creatorcontrib>Tan, Lei</creatorcontrib><creatorcontrib>Shen, Bin</creatorcontrib><creatorcontrib>Luo, Cheng</creatorcontrib><creatorcontrib>McNerney, Megan E</creatorcontrib><creatorcontrib>Chmura, Steven J</creatorcontrib><creatorcontrib>Arina, Ainhoa</creatorcontrib><creatorcontrib>Pitroda, Sean</creatorcontrib><creatorcontrib>He, Chuan</creatorcontrib><creatorcontrib>Liang, Hua Laura</creatorcontrib><creatorcontrib>Weichselbaum, Ralph R</creatorcontrib><title>YTHDF1 loss in dendritic cells potentiates radiation-induced antitumor immunity via STING-dependent type I IFN production</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>The 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 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.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antigen presentation</subject><subject>Antitumor activity</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cathepsins</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Interferon</subject><subject>Interferon Type I - genetics</subject><subject>Interferon Type I - immunology</subject><subject>Interferon Type I - metabolism</subject><subject>Ionizing radiation</subject><subject>Lymphocytes</subject><subject>Melanoma</subject><subject>Melanoma, Experimental - genetics</subject><subject>Melanoma, Experimental - immunology</subject><subject>Melanoma, Experimental - metabolism</subject><subject>Melanoma, Experimental - pathology</subject><subject>Melanoma, Experimental - radiotherapy</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - immunology</subject><subject>Membrane Proteins - metabolism</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Radioimmunotherapy</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - immunology</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Tumors</subject><subject>Vaccines</subject><issn>1558-8238</issn><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><recordid>eNqNklFv0zAQxyMEYmPwwBdAlpAQPGT4Yqdxn9BU1i1o2iRWkHiyHNtpPSV2sJ1p_fa4YpQW9QH5wSff7_4--_5Z9hrwKUBVfPwyq4HBBIon2TGUJctZQdjTnfgoexHCHcZAaUmfZ0dkSoqypNVxtv6xuPw8B9S5EJCxSGmrvIlGIqm7LqDBRW2jEVEH5IVKgXE2N1aNUiskUiqOvfPI9P1oTVyjeyPQ7aK-vsiVHpJYqkZxPWhUo3p-jQbvUulG5GX2rBVd0K8e95Ps2_x8MbvMr24u6tnZVS4pkCKnjSobTKFhqlWkUloSUjYgWilBqokoi4owolRZgSwlKyRrMGtEIZUiiumGnGSffusOY9NrJVNDXnR88KYXfs2dMHw_Y82KL909B5hgmJIqKbx_VPDu56hD5L0Jm-8RVrsxcAKAKcYlwwl9-w9650Zv0_sSRSmZFhOgf6ml6DQ3tnXpYrkR5WesSEJTAJKo_AC11FanLp3VrUnHe_zpAT4tpXsjDxZ82CtITNQPcSnGEHh9-_X_2Zvv--y7HXalRRdXwXXjZurhoKj0yX5et9upAOYbZ_OtsxP7ZneMW_KPlckvcAvwbA</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Wen, Chuangyu</creator><creator>Wang, Liangliang</creator><creator>Piffkó, András</creator><creator>Chen, Dapeng</creator><creator>Yu, Xianbin</creator><creator>Zawieracz, Katarzyna</creator><creator>Bugno, Jason</creator><creator>Yang, Kaiting</creator><creator>Naccasha, Emile Z</creator><creator>Ji, Fei</creator><creator>Wang, Jiaai</creator><creator>Huang, Xiaona</creator><creator>Luo, Stephen Y</creator><creator>Tan, Lei</creator><creator>Shen, Bin</creator><creator>Luo, Cheng</creator><creator>McNerney, Megan E</creator><creator>Chmura, Steven J</creator><creator>Arina, Ainhoa</creator><creator>Pitroda, Sean</creator><creator>He, Chuan</creator><creator>Liang, Hua Laura</creator><creator>Weichselbaum, Ralph R</creator><general>American Society for Clinical Investigation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8340-5190</orcidid><orcidid>https://orcid.org/0000-0003-3864-8382</orcidid><orcidid>https://orcid.org/0000-0002-7508-8006</orcidid><orcidid>https://orcid.org/0000-0001-5300-6594</orcidid><orcidid>https://orcid.org/0000-0001-9328-5655</orcidid></search><sort><creationdate>20241201</creationdate><title>YTHDF1 loss in dendritic cells potentiates radiation-induced antitumor immunity via STING-dependent type I IFN production</title><author>Wen, Chuangyu ; Wang, Liangliang ; Piffkó, András ; Chen, Dapeng ; Yu, Xianbin ; Zawieracz, Katarzyna ; Bugno, Jason ; Yang, Kaiting ; Naccasha, Emile Z ; Ji, Fei ; Wang, Jiaai ; Huang, Xiaona ; Luo, Stephen Y ; Tan, Lei ; Shen, Bin ; Luo, Cheng ; McNerney, Megan E ; Chmura, Steven J ; Arina, Ainhoa ; Pitroda, Sean ; He, Chuan ; Liang, Hua Laura ; Weichselbaum, Ralph R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4132-4bd5b041b8dfd37dec335b1afcc1cd6a527383dd571c5c82c8b08ba2cdd3d8eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antigen presentation</topic><topic>Antitumor activity</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cathepsins</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Interferon</topic><topic>Interferon Type I - genetics</topic><topic>Interferon Type I - immunology</topic><topic>Interferon Type I - metabolism</topic><topic>Ionizing radiation</topic><topic>Lymphocytes</topic><topic>Melanoma</topic><topic>Melanoma, Experimental - genetics</topic><topic>Melanoma, Experimental - immunology</topic><topic>Melanoma, Experimental - metabolism</topic><topic>Melanoma, Experimental - pathology</topic><topic>Melanoma, Experimental - radiotherapy</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - immunology</topic><topic>Membrane Proteins - metabolism</topic><topic>Metastasis</topic><topic>Methods</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Radiation therapy</topic><topic>Radioimmunotherapy</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - immunology</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Tumors</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wen, Chuangyu</creatorcontrib><creatorcontrib>Wang, Liangliang</creatorcontrib><creatorcontrib>Piffkó, András</creatorcontrib><creatorcontrib>Chen, Dapeng</creatorcontrib><creatorcontrib>Yu, Xianbin</creatorcontrib><creatorcontrib>Zawieracz, Katarzyna</creatorcontrib><creatorcontrib>Bugno, Jason</creatorcontrib><creatorcontrib>Yang, Kaiting</creatorcontrib><creatorcontrib>Naccasha, Emile Z</creatorcontrib><creatorcontrib>Ji, Fei</creatorcontrib><creatorcontrib>Wang, Jiaai</creatorcontrib><creatorcontrib>Huang, Xiaona</creatorcontrib><creatorcontrib>Luo, Stephen Y</creatorcontrib><creatorcontrib>Tan, Lei</creatorcontrib><creatorcontrib>Shen, Bin</creatorcontrib><creatorcontrib>Luo, Cheng</creatorcontrib><creatorcontrib>McNerney, Megan E</creatorcontrib><creatorcontrib>Chmura, Steven J</creatorcontrib><creatorcontrib>Arina, Ainhoa</creatorcontrib><creatorcontrib>Pitroda, Sean</creatorcontrib><creatorcontrib>He, Chuan</creatorcontrib><creatorcontrib>Liang, Hua Laura</creatorcontrib><creatorcontrib>Weichselbaum, Ralph R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wen, Chuangyu</au><au>Wang, Liangliang</au><au>Piffkó, András</au><au>Chen, Dapeng</au><au>Yu, Xianbin</au><au>Zawieracz, Katarzyna</au><au>Bugno, Jason</au><au>Yang, Kaiting</au><au>Naccasha, Emile Z</au><au>Ji, Fei</au><au>Wang, Jiaai</au><au>Huang, Xiaona</au><au>Luo, Stephen Y</au><au>Tan, Lei</au><au>Shen, Bin</au><au>Luo, Cheng</au><au>McNerney, Megan E</au><au>Chmura, Steven J</au><au>Arina, Ainhoa</au><au>Pitroda, Sean</au><au>He, Chuan</au><au>Liang, Hua Laura</au><au>Weichselbaum, Ralph R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>YTHDF1 loss in dendritic cells potentiates radiation-induced antitumor immunity via STING-dependent type I IFN production</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>134</volume><issue>23</issue><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>1558-8238</issn><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>The 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 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.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>39325547</pmid><doi>10.1172/JCI181612</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8340-5190</orcidid><orcidid>https://orcid.org/0000-0003-3864-8382</orcidid><orcidid>https://orcid.org/0000-0002-7508-8006</orcidid><orcidid>https://orcid.org/0000-0001-5300-6594</orcidid><orcidid>https://orcid.org/0000-0001-9328-5655</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1558-8238 |
| ispartof | The Journal of clinical investigation, 2024-12, Vol.134 (23), p.1-13 |
| issn | 1558-8238 0021-9738 1558-8238 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11601937 |
| source | MEDLINE; PubMed Central; EZB Electronic Journals Library |
| subjects | Animal models Animals Antigen presentation Antitumor activity Cancer therapies Care and treatment Cathepsins Dendritic cells Dendritic Cells - immunology Dendritic Cells - metabolism Female Flow cytometry Health aspects Humans Immunotherapy Interferon Interferon Type I - genetics Interferon Type I - immunology Interferon Type I - metabolism Ionizing radiation Lymphocytes Melanoma Melanoma, Experimental - genetics Melanoma, Experimental - immunology Melanoma, Experimental - metabolism Melanoma, Experimental - pathology Melanoma, Experimental - radiotherapy Membrane Proteins - genetics Membrane Proteins - immunology Membrane Proteins - metabolism Metastasis Methods Mice Mice, Knockout Physiological aspects Proteins Radiation therapy Radioimmunotherapy RNA-Binding Proteins - genetics RNA-Binding Proteins - immunology RNA-Binding Proteins - metabolism Tumors Vaccines |
| title | YTHDF1 loss in dendritic cells potentiates radiation-induced antitumor immunity via STING-dependent type I IFN production |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T15%3A32%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=YTHDF1%20loss%20in%20dendritic%20cells%20potentiates%20radiation-induced%20antitumor%20immunity%20via%20STING-dependent%20type%20I%20IFN%20production&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Wen,%20Chuangyu&rft.date=2024-12-01&rft.volume=134&rft.issue=23&rft.spage=1&rft.epage=13&rft.pages=1-13&rft.issn=1558-8238&rft.eissn=1558-8238&rft_id=info:doi/10.1172/JCI181612&rft_dat=%3Cgale_pubme%3EA820589113%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3144392614&rft_id=info:pmid/39325547&rft_galeid=A820589113&rfr_iscdi=true |