{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:25Z","timestamp":1792790365202,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Cancer Biology","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Cancer Prevention and Research Institute of Texas","award":["Recruitment of Established Investigator Award RR220010 (J.W.H.)"],"award-info":[{"award-number":["Recruitment of Established Investigator Award RR220010 (J.W.H.)"]}],"id":[{"id":"https:\/\/ror.org\/0003xa228","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Research to Prevent Blindness, Inc.","award":["Senior Scientific Investigator Award (J.W.H.)"],"award-info":[{"award-number":["Senior Scientific Investigator Award (J.W.H.)"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Research to Prevent Blindness, Inc.","award":["Challenge Grant to University of Texas Southwestern Department of Ophthalmology"],"award-info":[{"award-number":["Challenge Grant to University of Texas Southwestern Department of Ophthalmology"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Research to Prevent Blindness, Inc.","award":["Unrestricted Grant to University of Miami Department of Ophthalmology"],"award-info":[{"award-number":["Unrestricted Grant to University of Miami Department of Ophthalmology"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of General Medical Sciences","award":["Grant to the Medical Scientist Training Program of University of Miami, T32 GM145462 (J.J.D.)"],"award-info":[{"award-number":["Grant to the Medical Scientist Training Program of University of Miami, T32 GM145462 (J.J.D.)"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NCI Cancer Center","award":["P30 CA142543 to University of Texas Southwestern Simmons Comprehensive Cancer Center"],"award-info":[{"award-number":["P30 CA142543 to University of Texas Southwestern Simmons Comprehensive Cancer Center"]}]},{"name":"NCI Cancer Center","award":["P30 CA240139 to University of Miami Sylvester Comprehensive Cancer Center"],"award-info":[{"award-number":["P30 CA240139 to University of Miami Sylvester Comprehensive Cancer Center"]}]},{"name":"NEI Center Core Grants","award":["P30 EY030413 to University of Texas Southwestern Department of Ophthalmology"],"award-info":[{"award-number":["P30 EY030413 to University of Texas Southwestern Department of Ophthalmology"]}]},{"name":"NEI Center Core Grants","award":["P30 EY014801 to University of Miami Department of Ophthalmology"],"award-info":[{"award-number":["P30 EY014801 to University of Miami Department of Ophthalmology"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Uveal melanoma (UM) is characterized by a small number of recurrent genetic alterations that determine metastatic propensity. BAP1 loss and\n                  <jats:italic>PRAME<\/jats:italic>\n                  expression define the dominant prognostic axes in UM, yet how they promote malignant progression remains unclear. We profiled 190,535 cells from normal uvea, uveal nevus, primary and metastatic UM using single-cell transcriptomics, T cell receptor sequencing, spatial transcriptomics and isogenic perturbation models. Normal melanocytes, nevus cells and UM cells formed a transcriptional continuum marked by loss of differentiation and emergence of neural crest-like, stress-responsive, hypoxic-glycolytic and immune-interacting states. BAP1 loss and\n                  <jats:italic>PRAME<\/jats:italic>\n                  expression imposed distinct but convergent immunoregulatory programs, inducing interferon and TNF\u2013NF-\u03baB signaling and MHC-I expression, with HLA-E showing the strongest response. These alterations were accompanied by macrophage and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell remodeling. PRAME-enriched tumor regions formed spatially organized niches enriched for macrophages and plasma cells. These findings define BAP1 loss and PRAME expression as distinct but convergent axes of tumor\u2013immune coevolution and nominate HLA-E as a candidate mediator of immune resistance.\n                <\/jats:p>","DOI":"10.64898\/2026.09.23.752454","type":"posted-content","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:05:13Z","timestamp":1790661913000},"source":"Crossref","is-referenced-by-count":0,"title":["BAP1 loss and\n                  <i>PRAME<\/i>\n                  expression converge to remodel the tumor\u2013immune ecosystem during uveal melanoma progression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-4272","authenticated-orcid":false,"given":"James J.","family":"Dollar","sequence":"first","affiliation":[{"name":"Bascom Palmer Eye Institute, Interdisciplinary Stem Cell Institute, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-7333","authenticated-orcid":false,"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1812-9860","authenticated-orcid":false,"given":"Mithalesh","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Sorouri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6197-2642","authenticated-orcid":false,"given":"Jeffim N.","family":"Kuznetsoff","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, Interdisciplinary Stem Cell Institute, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2612-9633","authenticated-orcid":false,"given":"Sebastian","family":"Salazar","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, Interdisciplinary Stem Cell Institute, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Cruz","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, Interdisciplinary Stem Cell Institute, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9125-1718","authenticated-orcid":false,"given":"Christina","family":"Decatur","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, Interdisciplinary Stem Cell Institute, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-3757","authenticated-orcid":false,"given":"Zelia M.","family":"Correa","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, Interdisciplinary Stem Cell Institute, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1104-9809","authenticated-orcid":false,"given":"J. 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