{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:12:06Z","timestamp":1779210726938,"version":"3.51.4"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["K12 CA90628-23"],"award-info":[{"award-number":["K12 CA90628-23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:p>\n                    Immunotherapy has been effective in many cancer types but has failed in multiple clinical trials in prostate cancers, with the underlying mechanisms remaining largely unclear. Here, we demonstrate that androgen receptor pathway inhibitor (ARPI) plus irradiation (IR) triggered robust anticancer immunity in prostate cancers in both patients and mice. We show that androgen-activated AR suppressed innate immune signaling by inducing inhibitor of nuclear factor kappa-B kinase subunit epsilon (\n                    <jats:italic>IKBKE<\/jats:italic>\n                    ) gene repression through HDAC2 interaction with an\n                    <jats:italic>IKBKE<\/jats:italic>\n                    enhancer RNA (\n                    <jats:italic>IKBKE<\/jats:italic>\n                    eRNA, or\n                    <jats:italic>IKBKE-e<\/jats:italic>\n                    ). ARPI treatment caused\n                    <jats:italic>IKBKE<\/jats:italic>\n                    derepression and enhanced an IR-induced innate immune response via action of RIG-I and MDA5 dsRNA sensors.\n                    <jats:italic>IKBKE-e<\/jats:italic>\n                    ablation largely enhanced innate immunity in prostate cancer cells in culture and anticancer immunity in mice. Our results revealed AR, HDAC2, and\n                    <jats:italic>IKBKE<\/jats:italic>\n                    eRNA as critical intrinsic immune suppressors in prostate cancer cells, suggesting that rejuvenating inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK\u03b5) signaling by targeting\n                    <jats:italic>IKBKE-e<\/jats:italic>\n                    is an actionable strategy to elicit synthetic anticancer immunity in immunologically \u201ccold\u201d cancers such as prostate cancer.\n                  <\/jats:p>","DOI":"10.1172\/jci190928","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:00:54Z","timestamp":1768503654000},"source":"Crossref","is-referenced-by-count":1,"title":["Reversing enhancer RNA\u2013mediated IKBKE gene repression enables synthetic anticancer immunity in prostate cancer models"],"prefix":"10.1172","volume":"136","author":[{"given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China."},{"name":"Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China."},{"name":"Department of Biochemistry and Molecular Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China."},{"name":"Department of Biochemistry and Molecular Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China."},{"name":"Department of Biochemistry and Molecular Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-0239","authenticated-orcid":true,"given":"Jacob J.","family":"Orme","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, and"},{"name":"Department of Oncology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9784-0481","authenticated-orcid":true,"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, and"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Children\u2019s Hospital, National Clinical Research Center for Child Health, Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3814-853X","authenticated-orcid":true,"given":"Sean S.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urologic Science and Technology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China."},{"name":"Department of Biochemistry and Molecular Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[{"name":"The First Hospital of Jiaxing, Jiaxing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-4826","authenticated-orcid":true,"given":"Liguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Rodriguez-Bravo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Domingo-Domenech","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, 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