{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:20:54Z","timestamp":1772119254633,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["HRB-EIA2002-002"],"award-info":[{"award-number":["HRB-EIA2002-002"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","award":["24889"],"award-info":[{"award-number":["24889"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"DOI":"10.1007\/s00262-025-04198-7","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T04:19:00Z","timestamp":1761193140000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of two distinct uveal melanoma subtypes based on the immune cell infiltration of the primary tumour"],"prefix":"10.1007","volume":"74","author":[{"given":"Konstantinos","family":"Panagiotidis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Owens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grainne","family":"Finegan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel","family":"Horgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanos","family":"Tsavdaridis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achilleas","family":"Floudas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"4198_CR1","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.2147\/OPTH.S113623","volume":"10","author":"K Mahendraraj","year":"2016","unstructured":"Mahendraraj K, Lau C, Lee I, Chamberlain R (2016) Trends in incidence, survival, and management of uveal melanoma: a population-based study of 7,516 patients from the Surveillance, Epidemiology, and End Results database (1973–2012). Clin Ophthalmol 10:2113\u20132119","journal-title":"Clin Ophthalmol"},{"key":"4198_CR2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1001\/archopht.124.1.54","volume":"124","author":"E Weis","year":"2006","unstructured":"Weis E (2006) The association between host susceptibility factors and uveal melanoma: a meta-analysis. Arch Ophthalmol 124:54","journal-title":"Arch Ophthalmol"},{"key":"4198_CR3","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1136\/bjophthalmol-2015-306810","volume":"99","author":"MT Andreoli","year":"2015","unstructured":"Andreoli MT, Mieler WF, Leiderman YI (2015) Epidemiological trends in uveal melanoma. Br J Ophthalmol 99:1550\u20131553","journal-title":"Br J Ophthalmol"},{"key":"4198_CR4","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.ophtha.2007.01.032","volume":"114","author":"G Virgili","year":"2007","unstructured":"Virgili G et al (2007) Incidence of uveal melanoma in Europe. Ophthalmology 114:2309-2315.e2","journal-title":"Ophthalmology"},{"key":"4198_CR5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000492391","volume":"5","author":"C Baily","year":"2019","unstructured":"Baily C et al (2019) Uveal melanoma in Ireland. Ocul Oncol Pathol 5:195\u2013204","journal-title":"Ocul Oncol Pathol"},{"key":"4198_CR6","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/eye.2016.275","volume":"31","author":"S Kaliki","year":"2017","unstructured":"Kaliki S, Shields CL (2017) Uveal melanoma: relatively rare but deadly cancer. Eye 31:241\u2013257","journal-title":"Eye"},{"key":"4198_CR7","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1167\/iovs.03-0538","volume":"44","author":"E Kujala","year":"2003","unstructured":"Kujala E, Ma\u00a8kitie T, Kivela\u00a8 T (2003) Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 44:4651","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"4198_CR8","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1136\/bjophthalmol-2020-317949","volume":"106","author":"G Garg","year":"2022","unstructured":"Garg G et al (2022) Patients presenting with metastases: stage IV uveal melanoma, an international study. Br J Ophthalmol 106:510\u2013517","journal-title":"Br J Ophthalmol"},{"key":"4198_CR9","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.2214\/ajr.157.6.1950883","volume":"157","author":"JG Lorigan","year":"1991","unstructured":"Lorigan JG, Wallace S, Mavligit GM (1991) The prevalence and location of metastases from ocular melanoma: imaging study in 110 patients. Am J Roentgenol 157:1279\u20131281","journal-title":"Am J Roentgenol"},{"key":"4198_CR10","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1001\/jamaophthalmol.2016.0903","volume":"134","author":"CL Decatur","year":"2016","unstructured":"Decatur CL et al (2016) Driver mutations in uveal melanoma: associations with gene expression profile and patient outcomes. JAMA Ophthalmol 134:728","journal-title":"JAMA Ophthalmol"},{"key":"4198_CR11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41467-017-02428-w","volume":"9","author":"MG Field","year":"2018","unstructured":"Field MG et al (2018) Punctuated evolution of canonical genomic aberrations in uveal melanoma. Nat Commun 9:116","journal-title":"Nat Commun"},{"key":"4198_CR12","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1126\/science.1194472","volume":"330","author":"JW Harbour","year":"2010","unstructured":"Harbour JW et al (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330:1410\u20131413","journal-title":"Science"},{"issue":"7","key":"4198_CR13","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1038\/bjc.2014.417","volume":"111","author":"H Kalirai","year":"2014","unstructured":"Kalirai H, Dodson A, Faqir S, Damato BE, Coupland SE (2014) Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing. Br J Cancer 111(7):1373\u20131380. https:\/\/doi.org\/10.1038\/bjc.2014.417","journal-title":"Br J Cancer"},{"key":"4198_CR14","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/PAS.0000000000002176","volume":"48","author":"S Kennedy","year":"2024","unstructured":"Kennedy S et al (2024) Prognostic value of BAP1 protein expression in uveal melanoma. Am J Surg Pathol 48:329\u2013336","journal-title":"Am J Surg Pathol"},{"key":"4198_CR15","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aax1738","volume":"5","author":"JN Kuznetsov","year":"2019","unstructured":"Kuznetsov JN et al (2019) BAP1 regulates epigenetic switch from pluripotency to differentiation in developmental lineages giving rise to BAP1-mutant cancers. Sci Adv 5:eaax1738","journal-title":"Sci Adv"},{"key":"4198_CR16","doi-asserted-by":"crossref","first-page":"6953","DOI":"10.1158\/0008-5472.CAN-08-0365","volume":"68","author":"KH Ventii","year":"2008","unstructured":"Ventii KH et al (2008) BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res 68:6953\u20136962","journal-title":"Cancer Res"},{"key":"4198_CR17","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1038\/s41418-022-01024-w","volume":"29","author":"S-A Lee","year":"2022","unstructured":"Lee S-A et al (2022) BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability. Cell Death Differ 29:2381\u20132398","journal-title":"Cell Death Differ"},{"key":"4198_CR18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2353\/jmoldx.2010.090220","volume":"12","author":"MD Onken","year":"2010","unstructured":"Onken MD, Worley LA, Tuscan MD, Harbour JW (2010) An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma. J Mol Diagn 12:461\u2013468","journal-title":"J Mol Diagn"},{"key":"4198_CR19","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1136\/bjophthalmol-2013-303867","volume":"98","author":"N Cassoux","year":"2014","unstructured":"Cassoux N et al (2014) Genome-wide profiling is a clinically relevant and affordable prognostic test in posterior uveal melanoma. Br J Ophthalmol 98:769\u2013774","journal-title":"Br J Ophthalmol"},{"key":"4198_CR20","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.ophtha.2012.02.017","volume":"119","author":"MD Onken","year":"2012","unstructured":"Onken MD et al (2012) Collaborative ocular oncology group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology 119:1596\u20131603","journal-title":"Ophthalmology"},{"key":"4198_CR21","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ccell.2017.07.003","volume":"32","author":"AG Robertson","year":"2017","unstructured":"Robertson AG et al (2017) Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell 32:204-220.e15","journal-title":"Cancer Cell"},{"key":"4198_CR22","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1136\/bjophthalmol-2021-319700","volume":"107","author":"AB Beasley","year":"2023","unstructured":"Beasley AB, Preen DB, McLenachan S, Gray ES, Chen FK (2023) Incidence and mortality of uveal melanoma in Australia (1982\u20132014). Br J Ophthalmol 107:406\u2013411","journal-title":"Br J Ophthalmol"},{"key":"4198_CR23","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.ophtha.2011.01.040","volume":"118","author":"AD Singh","year":"2011","unstructured":"Singh AD, Turell ME, Topham AK (2011) Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 118:1881\u20131885","journal-title":"Ophthalmology"},{"key":"4198_CR24","volume":"9","author":"V Gill","year":"2022","unstructured":"Gill V et al (2022) Trends in uveal melanoma presentation and survival during five decades: a nationwide survey of 3898 Swedish patients. Front Med 9:926034","journal-title":"Front Med"},{"key":"4198_CR25","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2022.101041","volume":"90","author":"ES Rantala","year":"2022","unstructured":"Rantala ES, Hernberg MM, Piperno-Neumann S, Grossniklaus HE, Kivel\u00e4 TT (2022) Metastatic uveal melanoma: the final frontier. Prog Retin Eye Res 90:101041","journal-title":"Prog Retin Eye Res"},{"key":"4198_CR26","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1200\/JCO.2017.74.1090","volume":"36","author":"RD Carvajal","year":"2018","unstructured":"Carvajal RD et al (2018) Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicenter, randomized trial (SUMIT). J Clin Oncol 36:1232\u20131239","journal-title":"J Clin Oncol"},{"key":"4198_CR27","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1158\/1078-0432.CCR-19-1223","volume":"26","author":"JJ Luke","year":"2020","unstructured":"Luke JJ et al (2020) Randomized phase II trial and tumor mutational spectrum analysis from cabozantinib versus chemotherapy in metastatic uveal melanoma (Alliance A091201). Clin Cancer Res 26:804\u2013811","journal-title":"Clin Cancer Res"},{"key":"4198_CR28","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1002\/cncr.30258","volume":"122","author":"AP Algazi","year":"2016","unstructured":"Algazi AP et al (2016) Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer 122:3344\u20133353","journal-title":"Cancer"},{"key":"4198_CR29","volume":"10","author":"L Zimmer","year":"2015","unstructured":"Zimmer L et al (2015) Phase II decog-study of Ipilimumab in pretreated and treatment-na\u00efve patients with metastatic uveal melanoma. PLoS ONE 10:e0118564","journal-title":"PLoS ONE"},{"key":"4198_CR30","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1056\/NEJMoa2304753","volume":"389","author":"JC Hassel","year":"2023","unstructured":"Hassel JC et al (2023) Three-year overall survival with Tebentafusp in metastatic uveal melanoma. N Engl J Med 389:2256\u20132266","journal-title":"N Engl J Med"},{"key":"4198_CR31","doi-asserted-by":"crossref","unstructured":"participants in the 1st Human Cell Atlas Jamboree et al. EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data. Genome Biol. 20, 63 (2019).","DOI":"10.1186\/s13059-019-1662-y"},{"key":"4198_CR32","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao Y et al (2024) Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol 42:293\u2013304","journal-title":"Nat Biotechnol"},{"key":"4198_CR33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"CS McGinnis","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ (2019) Doubletfinder: doublet detection in single-cell rna sequencing data using artificial nearest neighbors. Cell Syst 8:329-337.e4","journal-title":"Cell Syst"},{"key":"4198_CR34","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s13059-019-1874-1","volume":"20","author":"C Hafemeister","year":"2019","unstructured":"Hafemeister C, Satija R (2019) Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol 20:296","journal-title":"Genome Biol"},{"key":"4198_CR35","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1054\/bjoc.1999.0923","volume":"82","author":"K Sisley","year":"2000","unstructured":"Sisley K et al (2000) Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma. Br J Cancer 82:330\u2013338","journal-title":"Br J Cancer"},{"key":"4198_CR36","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.3389\/fonc.2019.01145","volume":"9","author":"MS Basile","year":"2019","unstructured":"Basile MS et al (2019) Immunobiology of uveal melanoma: state of the art and therapeutic targets. Front Oncol 9:1145","journal-title":"Front Oncol"},{"key":"4198_CR37","doi-asserted-by":"crossref","first-page":"172","DOI":"10.21037\/atm.2016.05.04","volume":"4","author":"M Oliva","year":"2016","unstructured":"Oliva M, Rullan AJ, Piulats JM (2016) Uveal melanoma as a target for immune-therapy. Ann Transl Med 4:172","journal-title":"Ann Transl Med"},{"key":"4198_CR38","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1186\/s12864-022-08586-6","volume":"23","author":"H Matsuo","year":"2022","unstructured":"Matsuo H, Kamatani T, Hamba Y, Boroevich KA, Tsunoda T (2022) Association between high immune activity and worse prognosis in uveal melanoma and low-grade glioma in TCGA transcriptomic data. BMC Genomics 23:351","journal-title":"BMC Genomics"},{"key":"4198_CR39","doi-asserted-by":"crossref","DOI":"10.4161\/21624011.2014.947169","volume":"8","author":"PL Triozzi","year":"2019","unstructured":"Triozzi PL et al (2019) Molecular profiling of primary uveal melanomas with tumor-infiltrating lymphocytes. Oncoimmunology 8:e947169","journal-title":"Oncoimmunology"},{"key":"4198_CR40","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1159\/000334576","volume":"4","author":"IHG Bronkhorst","year":"2012","unstructured":"Bronkhorst IHG, Jager MJ (2012) Uveal melanoma: the inflammatory microenvironment. J Innate Immun 4:454\u2013462","journal-title":"J Innate Immun"},{"key":"4198_CR41","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1245\/s10434-010-0985-4","volume":"17","author":"SB Edge","year":"2010","unstructured":"Edge SB, Compton CC (2010) The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471\u20131474","journal-title":"Ann Surg Oncol"},{"key":"4198_CR42","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1001\/jamaophthalmol.2019.5710","volume":"138","author":"M Mazloumi","year":"2020","unstructured":"Mazloumi M et al (2020) Accuracy of the cancer genome atlas classification vs american joint committee on cancer classification for prediction of metastasis in patients with Uveal Melanoma. JAMA Ophthalmol 138:260\u2013267","journal-title":"JAMA Ophthalmol"},{"key":"4198_CR43","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1056\/NEJMoa2103485","volume":"385","author":"P Nathan","year":"2021","unstructured":"Nathan P et al (2021) Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med 385:1196\u20131206","journal-title":"N Engl J Med"},{"key":"4198_CR44","volume":"13","author":"X Lv","year":"2022","unstructured":"Lv X, Ding M, Liu Y (2022) Landscape of infiltrated immune cell characterization in uveal melanoma to improve immune checkpoint blockade therapy. Front Immunol 13:848455","journal-title":"Front Immunol"},{"key":"4198_CR45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0210276","volume":"14","author":"MS Basile","year":"2019","unstructured":"Basile MS et al (2019) Differential modulation and prognostic values of immune-escape genes in uveal melanoma. PLoS ONE 14:e0210276","journal-title":"PLoS ONE"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-025-04198-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-025-04198-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-025-04198-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T17:20:11Z","timestamp":1763054411000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-025-04198-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["4198"],"URL":"https:\/\/doi.org\/10.1007\/s00262-025-04198-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7510282\/v1","asserted-by":"object"}]},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"assertion":[{"value":"1 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"343"}}