{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T09:34:49Z","timestamp":1793266489896,"version":"4.5.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Wenzhou Basic Public Welfare Research Project","award":["Y2023153"],"award-info":[{"award-number":["Y2023153"]}]},{"name":"Wenzhou Basic Public Welfare Research Project","award":["Y20240041"],"award-info":[{"award-number":["Y20240041"]}]},{"name":"Wenzhou Basic Public Welfare Research Project","award":["ZY2023024"],"award-info":[{"award-number":["ZY2023024"]}]},{"name":"Zhejiang Province Traditional Chinese Medicine Science and Technology Program Project","award":["2024ZL610"],"award-info":[{"award-number":["2024ZL610"]}]},{"name":"Zhejiang Province Traditional Chinese Medicine Science and Technology Program Project","award":["2026ZL0083"],"award-info":[{"award-number":["2026ZL0083"]}]},{"name":"Medical and Health Science Program of Zhejiang Province","award":["2025HY0552"],"award-info":[{"award-number":["2025HY0552"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Anaplastic thyroid carcinoma (ATC) is a lethal malignancy with a dismal prognosis and limited therapeutic options. Although immunotherapy has revolutionized the oncological landscape, the efficacy of Programmed Cell Death Protein 1 (PD-1) blockade as a monotherapy remains underwhelming in ATC. Consequently, identifying novel agents capable of triggering immunogenic cell death (ICD) to sensitize ATC to immune checkpoint inhibitors is a critical clinical priority.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>Through high-throughput screening of 3200 compounds, Zingiberen newsaponin (ZN) was identified as a lead anti-ATC agent. Its therapeutic efficacy was evaluated using ATC cell lines, patient-derived organoids, and xenograft models. Mechanistic investigations were conducted via pharmacological inhibition, genetic knockout, and Western blotting to examine the autophagy-pyroptosis axis. Furthermore, an immunocompetent murine ATC model was employed to assess the synergistic effects of ZN and anti-PD-1 therapy on the tumor immune microenvironment through immunohistochemical analysis of T-cell infiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      ZN exhibited potent antiproliferative activity against ATC cells with half-maximal inhibitory concentration values ranging from 1.95 to 2.98 \u03bcM. Morphological assessment and biochemical assays (Lactate dehydrogenase, interleukin-1 beta, and high mobility group box 1 release) confirmed that ZN induces Gasdermin E (GSDME)-mediated pyroptosis via the activation of caspase-3 and caspase-8. Importantly, genetic knockout of GSDME significantly attenuated the pyroptotic phenotype, corroborating the central role of GSDME in ZN-induced pyroptosis. Mechanistically, ZN-induced pyroptosis was found to be autophagy-dependent, as pharmacological inhibition of autophagy with chloroquine significantly reversed GSDME cleavage and cell death both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      . Consistently, ATG5 knockdown markedly rescued ZN-induced cell pyroptosis. Furthermore, ZN functioned as a potent inducer of ICD. In immunocompetent murine models, ZN treatment remodeled the tumor immune microenvironment by significantly increasing the infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Notably, the combination of ZN and anti-PD-1 therapy demonstrated superior synergistic antitumor efficacy compared with monotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Our study identifies ZN as a novel inducer of autophagy-mediated GSDME pyroptosis in ATC. By triggering ICD and recruiting CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, ZN sensitizes ATC to PD-1 blockade, offering a promising therapeutic strategy for this lethal disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256261493805","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:13:19Z","timestamp":1791432799000},"page":"1212-1225","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Zingiberen Newsaponin Enhances Antitumor Immunity in Anaplastic Thyroid Carcinoma Via Induction of Autophagy-Dependent Pyroptosis"],"prefix":"10.1177","volume":"36","author":[{"given":"Qing-xuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."},{"name":"Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong-xin","family":"Zou","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."},{"name":"Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Alberta Institute of Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8751-2556","authenticated-orcid":false,"given":"Ye-feng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."},{"name":"Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"You","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."},{"name":"Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-dong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."},{"name":"Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0325-5671","authenticated-orcid":false,"given":"Jin-miao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."},{"name":"Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 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