{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:56:11Z","timestamp":1791262571950,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K08950"],"award-info":[{"award-number":["JP20K08950"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Anaplastic thyroid cancer (ATC) is a rare but extremely aggressive malignancy responsible for most thyroid cancer\u2013related deaths. To elucidate molecular and immunological characteristics distinguishing ATC from aggressive papillary thyroid cancer (PTC), we performed single\u2010cell RNA sequencing on three ATC and three lethal PTC samples. ATC tumor cells exhibited enhanced inflammatory and immune\u2010related gene expression, and co\u2010activation of MAPK and PI3K pathways. Notably, p53 pathway activity was suppressed in ATC, alongside activation of angiogenic and immune\u2010evasion programs, indicating a shift from proliferation\u2010driven to immune\u2010evasion\u2013oriented signaling. Transcriptional network analysis revealed E2F family activation, including\n                    <jats:italic>E2F1<\/jats:italic>\n                    ,\n                    <jats:italic>E2F7<\/jats:italic>\n                    , and\n                    <jats:italic>E2F8<\/jats:italic>\n                    , suggesting CDK\u2013RB\u2013E2F axis dysregulation drives tumor dedifferentiation and proliferation, whereby p53 suppression unleashes E2F\u2010dependent transcriptional reprogramming. Immunoprofiling revealed CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in ATC showed elevated exhaustion signatures and high expression of inhibitory immune checkpoint molecules, accompanied by enhanced Treg\u2013CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell interactions, indicating a dual\u2010layered immunosuppressive mechanism involving both T\u2010cell exhaustion and enhanced Treg\u2010mediated suppression. In addition, we identified antigen\u2010presenting CAFs with altered CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell interactions. These findings delineate a comprehensive single\u2010cell landscape of ATC and demonstrate coordinated alterations in tumor\u2010intrinsic signaling and the tumor microenvironment during dedifferentiation, provide a foundation for developing rational combination immunotherapies tailored to the molecular and immunological landscape of thyroid cancer.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72261","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T03:54:20Z","timestamp":1788753260000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Transcriptome of Anaplastic Thyroid Cancer Reveals Immunosuppressive Tumor Microenvironment Remodeling"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-2589","authenticated-orcid":false,"given":"Saeko","family":"Tahara","sequence":"first","affiliation":[{"name":"Bioinformatics Laboratory, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Department of Immunology, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-130X","authenticated-orcid":false,"given":"Akiko","family":"Iguchi\u2010Manaka","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgery, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Doctoral Program in Medical Science, Comprehensive Human Sciences University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Department of Breast\u2010Thyroid\u2010Endocrine Surgery University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5630-5100","authenticated-orcid":false,"given":"Tomohei","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Breast\u2010Thyroid\u2010Endocrine Surgery University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-4858","authenticated-orcid":false,"given":"Akira","family":"Shibuya","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"R&amp;D Center for Innovative Drug Discovery University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-2342","authenticated-orcid":false,"given":"Kazuko","family":"Shibuya","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"R&amp;D Center for Innovative Drug Discovery University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1606-2762","authenticated-orcid":false,"given":"Haruka","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory, Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Laboratory for AI Biology RIKEN Center for Biosystems Dynamics Research  Kobe Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14041061"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0322"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.4019"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI169653"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28803-w"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.010"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01938-4"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2024.03.004"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106484"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01045-4"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf3657"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.173712"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037807"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10680-5"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2024.0266"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02391-6"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.050"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.015"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.76"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0373"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-21-0414"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0202"},{"issue":"16","key":"e_1_2_13_33_1","first-page":"E1600","article-title":"p53 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