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Adv."],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:p>Immune checkpoint therapies have shown limited efficacy in metastatic castration-resistant prostate cancer (mCRPC). The AMADEUS prostate expansion cohort (NCT03651271) evaluated the efficacy, safety, and biomarkers of escalating ipilimumab doses combined with nivolumab. Patients received ipilimumab 1 milligram per kilogram (mg\/kg)\u00a0+\u00a0nivolumab 360 mg (I1+N360), ipilimumab 3 mg\/kg\u00a0+\u00a0nivolumab 1 mg\/kg (I3+N1), or ipilimumab 5 mg\/kg\u00a0+\u00a0nivolumab 1 mg\/kg (I5+N1). Coprimary endpoints were 6-month disease control rate (DCR) and changes in tumoral CD8 percentage. Thirty-two patients were enrolled. DCRs were 33% (4 of 12) for I1+N360, 20% (1 of 5) for I3+N1, and 20% (3 of 15) for I5+N1. Across cohorts, tumoral CD8 percentage increased by a median of 5.0%. Although higher ipilimumab doses were tolerable, I1+N360 achieved similar disease control and immune activation with a more favorable safety profile. Early disease progression was associated with increased expression of a TREM2-associated myeloid gene signature, which was also significantly enriched in two independent prostate cancer datasets.<\/jats:p>","DOI":"10.1126\/sciadv.aee8730","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:59:24Z","timestamp":1792000764000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Immune biomarkers of response and resistance to ipilimumab and nivolumab in metastatic castration-resistant prostate cancer"],"prefix":"10.1126","volume":"12","author":[{"given":"Apostolia M.","family":"Tsimberidou","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9938-1331","authenticated-orcid":true,"given":"Christopher R.","family":"Cabanski","sequence":"additional","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8865-3548","authenticated-orcid":true,"given":"Alexandra","family":"Drakaki","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4688-0958","authenticated-orcid":true,"given":"Danny N.","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-1294","authenticated-orcid":true,"given":"Bilal A.","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5028-3833","authenticated-orcid":true,"given":"Sreyashi","family":"Basu","sequence":"additional","affiliation":[{"name":"James P. 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