{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:08:26Z","timestamp":1774616906757,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T00:00:00Z","timestamp":1671235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T00:00:00Z","timestamp":1671235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Cancer League Zurich"},{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>\nImmunotherapy using immune checkpoint inhibitors (ICI) has revolutionized cancer treatment in recent years, particularly in melanoma. While response to immunotherapy is associated with high tumor mutational burden (TMB), PD-L1 expression, and microsatellite instability in several cancers, tumors lacking these biomarkers can still respond to this treatment. Especially, mucosal melanoma, commonly exhibiting low TMB compared to cutaneous melanoma, may respond to immunotherapy with immune checkpoint inhibitors. Therefore, the aim of our study was to investigate novel biomarkers in mucosal melanoma that predict response to combined ipilimumab and nivolumab.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>\nWe investigated 10 tumor samples from 10 patients (three responders, seven non-responders) before treatment and six tumor samples from five patients after progression using a targeted Next Generation Sequencing (NGS) gene expression panel. The findings were corroborated with an independent method (i.e., immunohistochemical staining) on the same 10 tumor samples before treatment and, to increase the cohort, in addition on three tumor samples before treatment of more recent patients (one responder, two non-responders).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>\nWith the targeted gene expression panel, we found the three tumor testis antigens <jats:italic>CTAG1B<\/jats:italic> (<jats:italic>NY-ESO-1<\/jats:italic>), <jats:italic>MAGE-A3<\/jats:italic>, and <jats:italic>MAGE-A4<\/jats:italic> to be predominantly expressed in responding tumors. This marker panel was either not or not completely expressed in non-responders (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Using immunohistochemistry for all three markers, we could confirm the elevated expression in tumors responding to the ipilimumab\/nivolumab combination therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In conclusion, these three biomarkers await validation in a larger patient cohort and could be easily used in future routine diagnostics to predict the outcome of ipilimumab\/nivolumab combination therapy in mucosal melanoma patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-022-04514-z","type":"journal-article","created":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T06:02:40Z","timestamp":1671256960000},"page":"5645-5653","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Combinational expression of tumor testis antigens NY-ESO-1, MAGE-A3, and MAGE-A4 predicts response to immunotherapy in mucosal melanoma patients"],"prefix":"10.1007","volume":"149","author":[{"given":"Sandra N.","family":"Freiberger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Holzmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gr\u00e9goire B.","family":"Morand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"H\u00fcllner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell P.","family":"Levesque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Dummer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktor H.","family":"Koelzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels J.","family":"Rupp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,17]]},"reference":[{"key":"4514_CR1","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","volume":"373","author":"H Borghaei","year":"2015","unstructured":"Borghaei H, Paz-Ares L, Horn L et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. 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MPL has received project-specific research funding from Roche, Novartis, Oncobit, and Molecular Partners outside the scope of this work. Prof. Dummer has intermittent, project focused consulting and\/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer and touchIME outside the submitted work. SNF, DH, GBM, VHK, and NJR have no competing interests regarding this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Ethical approval was given by the cantonal ethics commission (BASEC 2020\u201301663, approved: 30 July 2020) and all patients signed written informed consent (BASEC PB_2017-00494, amendment approved: 25 July 2017).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}