{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:43:18Z","timestamp":1792190598708,"version":"4.4.0"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":57,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["CA255211"],"award-info":[{"award-number":["CA255211"]}]},{"name":"NIH","award":["CA249633"],"award-info":[{"award-number":["CA249633"]}]},{"name":"NIH","award":["CA50706"],"award-info":[{"award-number":["CA50706"]}]},{"name":"NIH","award":["CA255211,CA249633,CA50706"],"award-info":[{"award-number":["CA255211,CA249633,CA50706"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:p>\n                    Cancer cells present neoantigens dominantly through MHC class I (MHCI) to drive tumor rejection through cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. There is growing recognition that a subset of tumors express MHC class II (MHCII), causing recognition of antigens by TCRs of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells that contribute to the antitumor response. We found that mouse\n                    <jats:italic>\n                      Braf\n                      <jats:sup>V600E<\/jats:sup>\n                    <\/jats:italic>\n                    -driven anaplastic thyroid cancers (ATCs) responded markedly to the RAF plus MEK inhibitors dabrafenib and trametinib (dab\/tram) and that this was associated with upregulation of\n                    <jats:italic>MhcII<\/jats:italic>\n                    in cancer cells and increased CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration. A subset of recurrent tumors lost\n                    <jats:italic>MhcII<\/jats:italic>\n                    expression due to silencing of\n                    <jats:italic>Ciita<\/jats:italic>\n                    , the master transcriptional regulator of\n                    <jats:italic>MhcII<\/jats:italic>\n                    , despite preserved IFN-\u03b3 signal transduction, which could be rescued by EZH2 inhibition. Orthotopically implanted\n                    <jats:italic>\n                      Ciita\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      H2-Ab1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ATC cells into immune-competent mice became unresponsive to the MAPK inhibitors. Moreover, depletion of CD4\n                    <jats:sup>+<\/jats:sup>\n                    , but not CD8\n                    <jats:sup>+<\/jats:sup>\n                    , T cells also abrogated the response to dab\/tram. These findings implicate MHCII-driven CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation as a key determinant of the response of\n                    <jats:italic>Braf<\/jats:italic>\n                    -mutant ATCs to MAPK inhibition.\n                  <\/jats:p>","DOI":"10.1172\/jci191781","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T16:00:26Z","timestamp":1755619226000},"source":"Crossref","is-referenced-by-count":5,"title":["Loss of tumor cell MHC class II drives MAPK inhibitor insensitivity of BRAF-mutant anaplastic thyroid cancers"],"prefix":"10.1172","volume":"135","author":[{"given":"Vera","family":"Tiedje","sequence":"first","affiliation":[{"name":"Human Oncology and Pathogenesis Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyue","family":"Qin","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Yeon","family":"Im","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gnana P.","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Boucai","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-9835","authenticated-orcid":true,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jena D.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, and"},{"name":"University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6885-3742","authenticated-orcid":true,"given":"Alan L.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3873-315X","authenticated-orcid":true,"given":"Elisa","family":"de Stanchina","sequence":"additional","affiliation":[{"name":"Antitumor Assessment Core Facility and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D.","family":"Socci","sequence":"additional","affiliation":[{"name":"Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-3862","authenticated-orcid":true,"given":"Jian","family":"Jin","sequence":"additional","affiliation":[{"name":"Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences, and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald A.","family":"Ghossein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Knauf","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program,"},{"name":"Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Koche","sequence":"additional","affiliation":[{"name":"Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Fagin","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program,"},{"name":"Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1604958"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00789-4"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0654-5"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182786"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10582"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2017.07.030"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3200"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500090102"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature10755"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature13988"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091918"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120532"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06199-x"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0177"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa656"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0373"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85271"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01180"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.6785"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.12.014"},{"issue":"10","key":"B21","first-page":"1184","article-title":"Dabrafenib versus dabrafenib + trametinib in BRAF-mutated radioactive iodine refractory differentiated thyroid cancer: results of a randomized, phase 2, open-label multicenter trial","volume":"32","author":"Busaidy","year":"2022","journal-title":"Thyroid"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0036"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022567"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf3657"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0133"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI120966"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-21-0442"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu749"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11030402"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0483"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.069"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846255"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac199"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403247"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0735"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0118"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2479"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0474-7"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1176731"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036013"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-007736"},{"key":"B42","doi-asserted-by":"crossref","unstructured":"Kim KS, et al. MAPK\/ERK signaling in gliomas modulates interferon responses, T cell recruitment, microglia phenotype, and immune checkpoint blockade efficacy [preprint]. https:\/\/doi.org\/10.1101\/2024.09.11.612571 Posted on bioRxiv September 18, 2024","DOI":"10.1101\/2024.09.11.612571"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00260-2"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0036"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2407417"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02727"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.4019"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.6088"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.07.1725"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.4729"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02961"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00521-2"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.12.007"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/gene.20043"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1516407"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.8.994"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2688"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/191781\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:11:37Z","timestamp":1779210697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/191781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":57,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10,15]]},"published-print":{"date-parts":[[2025,10,15]]}},"alternative-id":["10.1172\/JCI191781"],"URL":"https:\/\/doi.org\/10.1172\/jci191781","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.01.27.635086","asserted-by":"object"}]},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,19]]},"article-number":"e191781"}}