{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:56:42Z","timestamp":1791439002579,"version":"4.3.3"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972685"],"award-info":[{"award-number":["81972685"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272783"],"award-info":[{"award-number":["82272783"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Immune checkpoint blockade (ICB) has demonstrated efficacy in clinical cancer therapy; however, a significant proportion of cancer patients do not respond to ICB. One contributing factor to this lack of response is the impairment of IFN\u2010\u03b3 signaling within cancer cells. A20 acts as a negative regulator of IFN\u2010\u03b3 signaling. Our study aimed to investigate the mechanism by which A20 exerts its negative regulatory effect on IFN\u2010\u03b3 signaling in hepatocellular carcinoma (HCC) cells. Bioinformatic analysis revealed that A20 expression in HCC cell lines is inversely associated with the activation of IFN\u2010\u03b3 signaling. Functional loss and gain experiments demonstrated that A20 inhibits IFN\u2010\u03b3 signaling in HCC cells. The interaction between A20 and STAT1 was assessed using Co\u2010Immunoprecipitation (Co\u2010IP) assays and bimolecular fluorescence complementation (BioFC) assays. Our results also indicated that A20 suppresses the expression of downstream molecules involved in IFN\u2010\u03b3 signaling, such as CXCL9, CXCL10, and HLA\u2010ABC, in HCC cells. Additionally, enforced expression of A20 in HCC cells inhibited anti\u2010tumor immunity in a mouse model of HCC. Bioinformatic analysis suggests that A20 may negatively regulate IFN\u2010\u03b3 signaling in HCC cells from human HCC cohorts. Collectively, our study uncovers a novel mechanism whereby A20 inhibits IFN\u2010\u03b3 signaling in HCC cells through direct binding with STAT1. These findings enhance our understanding of the regulatory mechanisms of IFN\u2010\u03b3 signaling in cancer cells and provide insights for designing strategies to enhance the effectiveness of ICB therapy.<\/jats:p>","DOI":"10.1111\/cas.70556","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:47:47Z","timestamp":1791438467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>A20<\/scp>\n                    Inhibits\n                    <scp>IFN<\/scp>\n                    \u2010\u03b3 Signaling in Hepatocellular Carcinoma Cells by Binding to\n                    <scp>STAT1<\/scp>\n                    , Compromising Anti\u2010Tumor Immunity"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2983-7674","authenticated-orcid":false,"given":"Yanlei","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Immunology and Shandong Key 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