{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:49:00Z","timestamp":1777009740374,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["113\u20132314\u2010B\u2010182A\u2010132"],"award-info":[{"award-number":["113\u20132314\u2010B\u2010182A\u2010132"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["113\u20132320\u2010B\u2010182A\u2010012"],"award-info":[{"award-number":["113\u20132320\u2010B\u2010182A\u2010012"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glioblastoma (GBM) recurs rapidly despite surgery and radiochemotherapy and is associated with profound natural killer (NK) cell dysfunction. Adoptive NK cell transfer has emerged as a plausible immunotherapy for GBM and is being tested clinically; however, its efficacy is limited by the suppressive tumor microenvironment, low NK infiltration, and metabolic exhaustion. 4\u2010Acetylantroquinonol B (4\u2010AAQB), a ubiquinone derivative purified from\n                    <jats:italic>Antrodia cinnamomea<\/jats:italic>\n                    , has demonstrated antitumor and anti\u2010inflammatory properties. These properties suggest that 4\u2010AAQB may rescue or enhance NK cell activity against GBM cells. Therefore, we evaluated the effects of 4\u2010AAQB on the cytotoxicity of NK\u201092 cells against human GBM cells using NK cell cytotoxicity assays. Treatment with 4\u2010AAQB significantly enhanced the cytotoxicity of NK\u201092 cells against GBM cells, without affecting normal MRC5 fibroblasts. Additionally, in a GBM xenograft mouse model, 4\u2010AAQB and NK\u201092 cells individually suppressed tumor growth, whereas their combination produced a synergistic antitumor effect without inducing liver or kidney toxicity. Bulk RNA sequencing of excised tumors revealed distinct differentially expressed genes in the combination group that were not shared with either monotherapy. Notably, the combined therapy upregulated immune effector genes involved in apoptotic cell clearance and NK cell maturation, while simultaneously downregulating key survival and resistance pathways. Furthermore, pathway analysis revealed suppression of autophagy and mitophagy, suggesting that 4\u2010AAQB sensitizes GBM cells to immune\u2010mediated apoptosis by disrupting intrinsic survival circuits. These findings support 4\u2010AAQB as an orally administered adjuvant that enhances NK cell immunotherapy for GBM and warrant further translational development.\n                  <\/jats:p>","DOI":"10.1002\/cam4.71832","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:56:52Z","timestamp":1776484612000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Product 4\u2010Acetylantroquinonol B Enhances\n                    <scp>NK<\/scp>\n                    Cell\u2010Mediated Immunity Against Glioblastoma"],"prefix":"10.1002","volume":"15","author":[{"given":"Yuan\u2010Chieh","family":"Yeh","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine Chang Gung Memorial Hospital  Keelung Taiwan"},{"name":"Program in Molecular Medicine, College of Life Sciences National Yang Ming Chiao Tung University  Taipei 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