{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:14:09Z","timestamp":1789193649270,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873112"],"award-info":[{"award-number":["81873112"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The efficacy of anti\u2010PD\u20101 therapy is not as expected in hepatocellular carcinoma (HCC). YAP1 was overexpressed and activated in HCC. The mechanism of YAP1 in HCC immune escape is unclear. Anti\u2010PD\u20101 treatment increased YAP1 expression in liver tumor cells, and exhausted CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells in the blood and spleen of liver tumor mice. <jats:italic>YAP1<\/jats:italic> knockdown suppressed PD\u2010L1 expression, which was involved in JAK1\/STAT1, 3 pathways. Moreover, <jats:italic>Yap1<\/jats:italic> knockout elevated CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells in liver tumor niche. Consistently, verteporfin, YAP1 inhibitor, decreased TGF\u2010\u03b2 and IFN\u2010\u03b3 in liver tumor niche and exhausted CD8<jats:sup>+<\/jats:sup> T cell in the spleen. DHA suppressed YAP1 expression and break immune evasion in liver tumor niche, characterized by decreased PD\u2010L1 in liver tumor cells and increased CD8<jats:sup>+<\/jats:sup> T cell infiltration. Furthermore, DHA combined with anti\u2010PD\u20101 treatment promoted CD4<jats:sup>+<\/jats:sup> T cell infiltration in the spleen and CD8<jats:sup>+<\/jats:sup> T cell in tumor tissues of mice. In summary, <jats:italic>YAP1<\/jats:italic> knockdown in liver tumor cells suppressed PD\u2010L1 expression and recruited cytotoxic T lymphocytes (CTLs), leading to break immune evasion in tumor niche. Mechanistically, <jats:italic>YAP1<\/jats:italic> knockdown suppressed PD\u2010L1 expression, which was involved in JAK1\/STAT1, 3 pathways. Finally, DHA inhibited YAP1 expression, which not only inhibited liver tumor proliferation but also break the immunosuppressive niche in liver tumor tissues and improve the effect of anti\u2010PD\u20101 therapy.<\/jats:p>","DOI":"10.1002\/ptr.7695","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T14:08:57Z","timestamp":1672236537000},"page":"1740-1753","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Dihydroartemisinin broke the tumor immunosuppressive microenvironment by inhibiting <scp>YAP1<\/scp> expression to enhance <scp>anti\u2010PD<\/scp>\u20101 efficacy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2238-8400","authenticated-orcid":false,"given":"Qing","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Pathobiology and Immunology Hebei University of Chinese Medicine  Shijiazhuang 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