{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:44:55Z","timestamp":1790660695870,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Clinical Research Trust (CCRT) and HRB Summer Scholarship","award":["SS-2016-1806"],"award-info":[{"award-number":["SS-2016-1806"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Molecular and histopathological analysis of melanoma subtypes has revealed distinct epidemiological, genetic, and clinical features. However, immunotherapy for advanced metastatic melanoma patients does not differ based on subtype. Response to immune checkpoint inhibitors (ICI) has been shown to vary, therefore, predictive biomarkers are needed in the design of precision treatments. Targeted sequencing and histopathological analysis (CD8 and CD20 immunohistochemistry) were performed on subtypes of metastatic melanoma (cutaneous melanoma (CM, n = 10); head and neck melanoma (HNM, n = 7); uveal melanoma (UM, n = 4); acral lentiginous melanoma (AM, n = 1) and mucosal melanoma (MM, n = 1) treated with ICI). Progression-free survival (PFS) was significantly associated with high CD8 expression (p = 0.025) and mutations in DNA damage repair (DDR) pathway genes (p = 0.012) in all subtypes but not with CD20 expression. Our study identified that immune cell infiltration and DDR gene mutations may have an impact in response to ICI treatment in metastatic melanoma but differs among subtypes. Therefore, a comprehensive understanding of the immune infiltration cells\u2019 role and DDR gene mutations in metastatic melanoma may identify prognostic biomarkers.<\/jats:p>","DOI":"10.3390\/medsci10020026","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T03:16:55Z","timestamp":1653362215000},"page":"26","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical Impact of Immune Checkpoint Inhibitor (ICI) Response, DNA Damage Repair (DDR) Gene Mutations and Immune-Cell Infiltration in Metastatic Melanoma Subtypes"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-5025","authenticated-orcid":false,"given":"Charlotte","family":"Andrieu","sequence":"first","affiliation":[{"name":"National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Glasnevin, D09 E432 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"McNamee","sequence":"additional","affiliation":[{"name":"National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Glasnevin, D09 E432 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Larkin","sequence":"additional","affiliation":[{"name":"National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Glasnevin, D09 E432 Dublin, Ireland"},{"name":"Department of Life Sciences, Institute of Technology Sligo, F91 YW50 Sligo, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1193-5528","authenticated-orcid":false,"given":"Alanna","family":"Maguire","sequence":"additional","affiliation":[{"name":"National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Glasnevin, D09 E432 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roopika","family":"Menon","sequence":"additional","affiliation":[{"name":"Siemens Healthcare Diagnostics Products GmbH, 50667 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Mueller-Eisert","sequence":"additional","affiliation":[{"name":"Siemens Healthcare Diagnostics Products GmbH, 50667 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Horgan","sequence":"additional","affiliation":[{"name":"Royal Victoria Eye and Ear Hospital, Adelaide Road, D02 XK51 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Royal Victoria Eye and Ear Hospital, Adelaide Road, D02 XK51 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Gullo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, St. Vincent\u2019s University Hospital, D04 T6F4 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Crown","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, St. Vincent\u2019s University Hospital, D04 T6F4 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-3564","authenticated-orcid":false,"given":"Naomi","family":"Walsh","sequence":"additional","affiliation":[{"name":"National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Glasnevin, D09 E432 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N. 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