{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:07:35Z","timestamp":1789214855123,"version":"build-2803163510"},"reference-count":43,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100016229","name":"Basic Research Laboratory","doi-asserted-by":"crossref","award":["ZIA BC 011191"],"award-info":[{"award-number":["ZIA BC 011191"]}],"id":[{"id":"10.13039\/100016229","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Anaplastic thyroid cancer (ATC) is a highly lethal malignancy with poor survival and limited therapeutic options. The mechanisms driving immune evasion in ATC remain poorly understood. The cyclic GMP\u2013AMP synthase\u2013stimulator of interferon genes (cGAS\u2013STING) pathway is a key mediator of innate immune sensing and antitumor immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We investigated the role of cGAS\u2013STING signaling in ATC using three complementary models (i) a genetically engineered mouse model harboring triple mutations in\n                      <jats:italic toggle=\"yes\">Thrb1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Trp53<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Pten<\/jats:italic>\n                      (RU3 model); (ii) an orthotopic tumor model derived from\n                      <jats:italic toggle=\"yes\">Trp53<\/jats:italic>\n                      - and\n                      <jats:italic toggle=\"yes\">Braf<\/jats:italic>\n                      -mutant ATC cells; and (iii) subcutaneous tumor models of\n                      <jats:italic toggle=\"yes\">Ifnb1<\/jats:italic>\n                      - or\n                      <jats:italic toggle=\"yes\">Trp53<\/jats:italic>\n                      -expressing ATC cells. Tumor immune microenvironment alterations were assessed using comprehensive molecular approaches, including single-cell RNA sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The models demonstrated marked suppression of cGAS\u2013STING signaling during ATC progression. This suppression was associated with impaired antitumor immunity, characterized by reduced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration and diminished type I interferon (IFN-I) responses. Restoration of IFN\u03b21 signaling in ATC cells significantly enhanced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell recruitment and inhibited tumor growth\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      . These findings indicate that immune evasion in ATC is driven by decreased IFN\u03b21 production rather than resistance to its downstream effects. Mechanistically, p53 was found to sustain cGAS\u2013STING\u2013IFN\u03b21-mediated antitumor immunity, and its loss contributed to reduced IFN\u03b21 expression and immune escape.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Impaired DNA sensing via suppression of the cGAS\u2013STING\u2013IFN\u03b21 axis promotes immune evasion in ATC. Therapeutic strategies aimed at restoring this pathway may enhance antitumor immunity and represent a promising approach for treating this aggressive disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256261481666","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:51:50Z","timestamp":1787745110000},"page":"1074-1084","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Suppressed cGAS\u2013STING DNA Sensing Drives Immune Evasion in Anaplastic Thyroid Cancer"],"prefix":"10.1177","volume":"36","author":[{"given":"Xu-guang","family":"Zhu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5186-5990","authenticated-orcid":false,"given":"Manju","family":"Acharya","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunmi","family":"Hwang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8882-3401","authenticated-orcid":false,"given":"Nathan","family":"Wong","sequence":"additional","affiliation":[{"name":"CCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA."},{"name":"Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naris","family":"Nilubol","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Section, Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3530-2386","authenticated-orcid":false,"given":"Sheue-yann","family":"Cheng","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI169653"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0373"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85271"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.25634"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.21.00504"},{"issue":"7","key":"e_1_3_3_7_1","first-page":"1454","article-title":"High prevalence of BRAF mutations in thyroid cancer: Genetic evidence for constitutive activation of the RET\/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma","volume":"63","author":"Kimura ET","year":"2003","unstructured":"6.Kimura ET, , Nikiforova MN, , Zhu Z, et al. High prevalence of BRAF mutations in thyroid cancer: Genetic evidence for constitutive activation of the RET\/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. 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