Muyi Yang, Suzanne Egyhazi Brage, Jan Lapins, Vitali Grozman, Fernanda Costa Svedman, Veronica Höiom, Hildur Helgadottir
{"title":"Germline MC1R Variant Status and Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Melanoma","authors":"Muyi Yang, Suzanne Egyhazi Brage, Jan Lapins, Vitali Grozman, Fernanda Costa Svedman, Veronica Höiom, Hildur Helgadottir","doi":"10.1111/pcmr.70050","DOIUrl":null,"url":null,"abstract":"<p>The melanocortin-1-receptor (MC1R<i>)</i> has a key role in melanocyte pigmentation regulation. Certain <i>MC1R</i> germline genetic variants (<i>R</i> alleles) result in deficient melanin production and are associated with red hair, freckling, UV sensitivity, and melanoma susceptibility. We aimed to address whether inherited polymorphisms in <i>MC1R</i> impact the efficacy of immune checkpoint inhibitors (ICI) in patients with metastatic melanoma. Patients with advanced melanoma undergoing ICI treatment were genotyped for <i>MC1R</i> variants. The patients were grouped by their germline <i>MC1R R</i> variants (≥ 1 or 0) and followed for treatment response, progression-free survival (PFS) and overall survival (OS). Of the 103 patients included, 39 (37.9%) had at least one <i>MC1R R</i> allele (<i>MC1R</i>-R-carriers), whereas 64 patients did not harbor any <i>R</i> allele (<i>MC1R</i>-R-non-carriers). The hazard ratio (HR) for PFS in <i>MC1R</i>-R-carriers was 0.60, (95% CI 0.37–0.98, <i>p</i> = 0.043). The HR for OS was 0.63 (95% CI 0.37–1.08, <i>p</i> = 0.091). While <i>MC1R</i> is closely associated with melanoma susceptibility, its impact on ICI efficacy has not been explored previously. <i>MC1R</i>-R-carriers with metastatic melanoma had improved PFS when treated with ICIs. If validated in larger cohorts, <i>MC1R</i> genotyping may serve as a factor helping to predict response to ICIs in melanoma patients.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70050","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pigment Cell & Melanoma Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/pcmr.70050","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The melanocortin-1-receptor (MC1R) has a key role in melanocyte pigmentation regulation. Certain MC1R germline genetic variants (R alleles) result in deficient melanin production and are associated with red hair, freckling, UV sensitivity, and melanoma susceptibility. We aimed to address whether inherited polymorphisms in MC1R impact the efficacy of immune checkpoint inhibitors (ICI) in patients with metastatic melanoma. Patients with advanced melanoma undergoing ICI treatment were genotyped for MC1R variants. The patients were grouped by their germline MC1R R variants (≥ 1 or 0) and followed for treatment response, progression-free survival (PFS) and overall survival (OS). Of the 103 patients included, 39 (37.9%) had at least one MC1R R allele (MC1R-R-carriers), whereas 64 patients did not harbor any R allele (MC1R-R-non-carriers). The hazard ratio (HR) for PFS in MC1R-R-carriers was 0.60, (95% CI 0.37–0.98, p = 0.043). The HR for OS was 0.63 (95% CI 0.37–1.08, p = 0.091). While MC1R is closely associated with melanoma susceptibility, its impact on ICI efficacy has not been explored previously. MC1R-R-carriers with metastatic melanoma had improved PFS when treated with ICIs. If validated in larger cohorts, MC1R genotyping may serve as a factor helping to predict response to ICIs in melanoma patients.
期刊介绍:
Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords
Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders