https://m2.mtmt.hu/ hun 2026-10-25 09:10 JournalArticle 32099890 VALIDATED true Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, AT-1090, Austria Institute of Cancer Research, Medical University of Vienna, Vienna, AT-1090, Austria Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, AT-1090, Austria Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, AT-1030, Austria Division Pharmacology, Department of Pharmacology, Physiology and Microbiology, Karl Landsteiner University of Health Sciences, Krems, AT-3500, Austria Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, AT-1210, Austria De-partment of Laboratory Medicine, Medical University of Vienna, Vienna, AT-1090, Austria Core Facilities, Medical University of Vienna, Vienna, AT-1090, Austria Division of Vascular and Endovascular Surgery, Center for Vascular Biology Research, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States Transplant Institute, Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, AT-1090, Austria 1st Department of Tumor Biology, National Korányi Institute of Pulmonology, Semmelweis University, Budapest, HU-1121, Hungary Department of Thoracic Surgery, National Institute of Oncology, Semmelweis University, Budapest, HU-1122, Hungary MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, 2nd Department of Pediatrics, Semmelweis University, Budapest, HU-1117, Hungary Department of Bioinformatics, Semmelweis University, Budapest, HU-1094, Hungary 2nd Department of Pediatrics, Semmelweis University, Budapest, HU-1094, Hungary 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, HU-1085, Hungary 1st Department of Pulmonology, National Korányi Institute of Pulmonology, Budapest, HU-1121, Hungary SE-NAP Brain Metastasis Research Group, 2nd Department of Pathology, Semmelweis University, Budapest, HU-1122, Hungary Cited By :1 Export Date: 10 October 2022 Correspondence Address: Moll, H.P.; Institute of Pharmacology, Austria; email: herwig.moll@meduniwien.ac.at 0 false 2026-10-21T12:55:40.665+0000 2025-11-14T16:55:02.240+0000 2021-07-11T09:10:54.450+0000 true 10003072 Moldvay Judit /api/author/10003072 Author true 10003072 2026-07-21T12:15:15.301+0000 2023-10-12T14:29:10.030+0000 true 10073918 Kovács Marcell /api/admin/10073918 Admin true Admin 10073918 /api/admin/10073918 Kovács Marcell true true 2023-10-04T07:54:51.165+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Breitenecker, Kristina Down-regulation of A20 promotes immune escape of lung adenocarcinomas true true /api/journal/10015757 REVIEWED true false 10015757 false 10015757 true 1946-6234 1946-6242 Journal FOREIGN 13 601 eabc3911 eabc3911 15 2021 Inflammation is a well-known driver of lung tumorigenesis. One strategy by which tumor cells escape tight homeostatic control is by decreasing the expression of the potent anti-inflammatory protein tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20. We observed that tumor cell intrinsic loss of A20 markedly enhanced lung tumorigenesis and was associated with reduced CD8+ T cell-mediated immune surveillance in patients with lung cancer and in mouse models. In mice, we observed that this effect was completely dependent on increased cellular sensitivity to interferon-gamma (IFN-gamma) signaling by aberrant activation of TANK-binding kinase 1 (TBK1) and increased downstream expression and activation of signal transducer and activator of transcription 1 (STAT1). Interrupting this autocrine feed forward loop by knocking out IFN-alpha/beta receptor completely restored infiltration of cytotoxic T cells and rescued loss of A20 depending tumorigenesis. Downstream of STAT1, programmed death ligand 1 (PD-L1) was highly expressed in A20 knockout lung tumors. Accordingly, immune checkpoint blockade (ICB) treatment was highly efficient in mice harboring A20-deficient lung tumors. Furthermore, an A20 loss-of-function gene expression signature positively correlated with survival of melanoma patients treated with anti-programmed cell death protein 1. Together, we have identified A20 as a master immune checkpoint regulating the TBK1-STAT1-PD-L1 axis that may be exploited to improve ICB therapy in patients with lung adenocarcinoma. Funding 2007897 /api/funding/2007897 false true Funding 2007898 /api/funding/2007898 false true Funding 2007899 /api/funding/2007899 false true true true 2021 true true true false true false NONE 2026-10-21 false 36 0 36 31 0 36 33 34 28 36 36 31 31 31 5 0 36 31 36 31 0 3 3 Folyóiratcikk Journal Article 24 35 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 1 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2022 0 4 4 4 4 2023 0 5 3 5 3 2024 0 10 9 10 9 2025 0 11 9 11 9 2026 0 6 6 6 6 D1 false 10003072 false false false 2021-07-12T09:09:41.520+0000 Bioinformatika Tanszék (SE / AOK / I); I. Sz. Patológiai és Kísérleti Rákkutató Intézet (SE / AOK / I); II. Sz. Gyermekgyógyászati Klinika (SE / AOK / K); MTA-SE-NAP B Agymetasztázis Kutatócsoport (SE / AOK / I / IISZPI); Mellkassebészeti Klinika (SE / AOK / K); Onkológiai Biomarker Kutatócsoport (Lendület) (HRN TTK / MÉI) 5 48 6 24 0 true 10073918 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 96785002 /api/authorship/96785002 1 0.041666668 true false false Breitenecker Kristina true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96785003 /api/authorship/96785003 2 0.042 true false false Homolya Monika true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96785004 /api/authorship/96785004 3 0.042 true false false Luca Andreea C. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96785005 /api/authorship/96785005 4 0.041666668 false false false Lang Veronika true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true 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true Győrffy Balázs true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96785022 /api/authorship/96785022 21 0.041666668 false false false Author 10024599 /api/author/10024599 Dezső Katalin true 10024599 true Dezso Katalin true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96785023 /api/authorship/96785023 22 0.042 false false false Author 10003072 /api/author/10003072 Moldvay Judit true 10003072 true Moldvay Judit true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96785024 /api/authorship/96785024 23 0.041666668 false false false Casanova Emilio true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 96785025 /api/authorship/96785025 24 0.042 false true true Moll Herwig P. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PublicationIdentifier 19004613 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Reference 21703091 /api/reference/21703091 77 10.1038/nature09881 false true Reference 21703092 /api/reference/21703092 78 10.1023/B:BILE.0000019559.84305.47 false true Reference 21703093 /api/reference/21703093 79 10.1093/bioinformatics/bts635 false true Reference 21703094 /api/reference/21703094 80 10.1186/s13059-014-0550-8 false true Reference 21703095 /api/reference/21703095 81 10.1093/nar/gkw419 false true /api/publication/32099890 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Breitenecker Kristina </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Homolya Monika<sup>*</sup> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Luca Andreea C.<sup>*</sup> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Lang Veronika </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Trenk Christoph </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Petroczi Georg </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Mohrherr Julian </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Horvath Jaqueline </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Moritsch Stefan </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Haas Lisa </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kurnaeva Margarita </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Eferl Robert </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Stoiber Dagmar </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Moriggl Richard </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Bilban Martin </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Obenauf Anna C. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ferran Christiane </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000046"><a href="/gui2/?type=authors&mode=browse&sel=10000046" target="_blank">Dome Balazs (<span class="authorship-author-name">Döme Balázs</span> <span class="authorAux-mtmt"> Tumor indukált angiogenezis</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/Mellkassebészeti Klinika</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10037177"><a href="/gui2/?type=authors&mode=browse&sel=10037177" target="_blank">Laszlo Viktoria (<span class="authorship-author-name">László Viktória</span> <span class="authorAux-mtmt"> tumorbiologia</span>) </a> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000109"><a href="/gui2/?type=authors&mode=browse&sel=10000109" target="_blank">Győrffy Balázs (<span class="authorship-author-name">Győrffy Balázs</span> <span class="authorAux-mtmt"> Onkológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/II. Sz. Gyermekgyógyászati Klinika; <span title="Természettudományi Kutatóközpont">TTK</span>/<span title="Enzimológiai Intézet">EI</span>/Onkológiai Biomarker Kutatócsoport (Lendület); <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Bioinformatika Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10024599"><a href="/gui2/?type=authors&mode=browse&sel=10024599" target="_blank">Dezso Katalin (<span class="authorship-author-name">Dezső Katalin</span> <span class="authorAux-mtmt"> Patológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/I. Sz. Patológiai és Kísérleti Rákkutató Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10003072"><a href="/gui2/?type=authors&mode=browse&sel=10003072" target="_blank">Moldvay Judit (<span class="authorship-author-name">Moldvay Judit</span> <span class="authorAux-mtmt"> Tüdõgyógyászat</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="II. Sz. Patológiai Intézet">IISZPI</span>/MTA-SE-NAP B Agymetasztázis Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Casanova Emilio </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Moll Herwig P. ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32099890" target="_blank">Down-regulation of A20 promotes immune escape of lung adenocarcinomas</a></div> <div> <span class="journal-title">SCIENCE TRANSLATIONAL MEDICINE</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1946-6234">1946-6234</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1946-6242">1946-6242</a>)</span>: <span class="journal-volume">13</span> <span class="journal-issue">601</span> <span class="page"> Paper eabc3911. 15 p. </span> <span class="year">(2021)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1126/scitranslmed.abc3911" target="_blank" href="https://doi.org/10.1126/scitranslmed.abc3911"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000678119700004" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000678119700004"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85109458225" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85109458225"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="34233950" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=34233950&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 36</span> | Független: 31 | Függő: 5 | Nem jelölt: 0 | WoS jelölt: 34 | Scopus jelölt:&nbsp;28 | WoS/Scopus jelölt:&nbsp;36 | DOI jelölt:&nbsp;33 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32099890&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 3 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32099890</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (KH129581) Támogató: NKFIH, (ÚNKP-19-4), (K129065) </div> <div class="lastModified">Utolsó módosítás: 2025.11.14. 17:55 Vasvari Lilian (MTMT Központ, admin) </div> <div class="lockedBy">Központi kezelésű 2023.10.04. 09:54 Kovács Marcell (MTMT Közp., admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, AT-1090, Austria Institute of Cancer Research, Medical University of Vienna, Vienna, AT-1090, Austria Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, AT-1090, Austria Research Institute of Molecul...</pre> </div></div>