Muyi Yang, Suzanne Egyhazi Brage, Jan Lapins, Vitali Grozman, Fernanda Costa Svedman, Veronica Höiom, Hildur Helgadottir
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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":"{\"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). 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引用次数: 0
摘要
黑素皮质素-1受体(melanocortin-1 receptor, MC1R)在黑素细胞色素沉着调节中起关键作用。某些MC1R种系遗传变异(R等位基因)导致黑色素产生不足,并与红头发、雀斑、紫外线敏感性和黑色素瘤易感性有关。我们的目的是研究MC1R遗传多态性是否会影响免疫检查点抑制剂(ICI)在转移性黑色素瘤患者中的疗效。接受ICI治疗的晚期黑色素瘤患者进行MC1R变异基因分型。根据患者的种系MC1R R变异(≥1或0)对患者进行分组,并随访治疗反应、无进展生存期(PFS)和总生存期(OS)。在纳入的103例患者中,39例(37.9%)至少有一个MC1R R等位基因(MC1R-R携带者),而64例患者没有任何R等位基因(MC1R-R非携带者)。mc1r - r携带者PFS的风险比(HR)为0.60,(95% CI 0.37 ~ 0.98, p = 0.043)。OS的HR为0.63 (95% CI 0.37 ~ 1.08, p = 0.091)。虽然MC1R与黑色素瘤易感性密切相关,但其对ICI疗效的影响尚未被探讨。mc1r - r携带的转移性黑色素瘤患者在接受ICIs治疗后PFS得到改善。如果在更大的队列中得到验证,MC1R基因分型可能有助于预测黑色素瘤患者对ICIs的反应。
Germline MC1R Variant Status and Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Melanoma
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