{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:08:27Z","timestamp":1793419707331,"version":"4.5.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020552","name":"Ministry of Higher Education, Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020552","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Uveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated  significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Evaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Our results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1225140","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T11:57:48Z","timestamp":1692359868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["The immune checkpoint VISTA is associated with prognosis in patients with malignant uveal melanoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Nour el Imane","family":"Issam Salah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Marnissi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhakim","family":"Lakhdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Karkouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"ElBelhadji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah","family":"Badou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e31824d09a8","article-title":"Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases","volume":"32","author":"Shields","year":"2012","journal-title":"Retina"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3614039","article-title":"Epidemiological study of uveal melanoma from US surveillance, epidemiology, and end results program (2010-2015)","volume":"2020","author":"Xu","year":"2020","journal-title":"J Ophthalmol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.4103\/0301-4738.154367","article-title":"Uveal melanoma: estimating prognosis","volume":"63","author":"Kaliki","year":"2015","journal-title":"Indian J Ophthalmol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.100800","article-title":"Uveal melanoma: Towards a molecular understanding","volume":"75","author":"Smit","year":"2020","journal-title":"Prog Retin Eye Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/IIO.0000000000000263","article-title":"Immune checkpoint inhibitors in uveal and conjunctival melanoma","volume":"59","author":"Wierenga","year":"2019","journal-title":"Int Ophthalmol Clin"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.432","article-title":"Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines","volume":"33","author":"Butt","year":"2014","journal-title":"Oncogene"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302369","article-title":"Nivolumab plus ipilimumab in advanced melanoma","volume":"369","author":"Wolchok","year":"2013","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30700-9","article-title":"Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial","volume":"19","author":"Hodi","year":"2018","journal-title":"Lancet Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/360136","article-title":"Genetics of uveal melanoma and cutaneous melanoma: two of a kind","volume":"2010","author":"Van den Bosch","year":"2010","journal-title":"Dermatol Res Pract"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0066","article-title":"PD L1 expression in tumor metastasis is different between uveal melanoma and cutaneous melanoma","volume":"9","author":"Javed","year":"2017","journal-title":"Immunotherapy"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2012.126","article-title":"Progress in the management of patients with uveal melanoma. 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