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在儿童和成人黑色素瘤中 NY-ESO-1、酪氨酸酶、MAGE-A3 和 TPTE 肿瘤抗原的表达：一项回顾性病例对照研究。

Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study.

机构信息

Department of Dermatology, Eberhard Karls University of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.

Institute for Immunobiology, Kantonsspital St Gallen, St Gallen, Switzerland.

出版信息

Virchows Arch. 2024 Aug;485(2):335-346. doi: 10.1007/s00428-024-03846-0. Epub 2024 Jun 18.

DOI:10.1007/s00428-024-03846-0
PMID:38890171
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11329550/
Abstract

Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma. Our main objective was to characterize expression of those TAAs in pediatric melanomas compared to control cohorts. In this retrospective case control study, protein and transcript expression of NY-ESO-1, tyrosinase, MAGE-A3, and TPTE were analyzed in a cohort of 25 pediatric melanomas, 31 melanomas of young adults, 29 adult melanomas, and 30 benign melanocytic nevi in children using immunohistochemical staining and digital pathology (QuPath) and reverse transcription quantitative PCR. Based on IHC analysis, pediatric melanomas expressed tyrosinase (100.0%), TPTE (44.0%), MAGE-A3 (12.0%), and NY-ESO-1 (8.0%). Young adult melanomas expressed tyrosinase (96.8%), NY-ESO-1 (19.4%), MAGE-A3 (19.4%), and TPTE (3.2%). Adult melanomas expressed tyrosinase (86.2%), MAGE-A3 (75.9%), NY-ESO-1 (48.3%), and TPTE (48.3%). Childhood melanocytic nevi only expressed tyrosinase (93.3%). Expression prevalence of individual TAAs did not differ between subtypes of pediatric melanoma, and no association with prognosis was found. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma.

摘要

肿瘤相关抗原（TAA）是皮肤黑色素瘤 T 细胞免疫治疗方法的潜在靶点。BNT111 是一种正在进行临床试验的研究性脂质体制剂 mRNA 基治疗性癌症疫苗，编码黑色素瘤 TAA NY-ESO-1、酪氨酸酶、MAGE-A3 和 TPTE，正在成人中进行临床测试。这些 TAA 在儿科黑色素瘤中的表达尚不清楚，但这是该治疗方法在儿童黑色素瘤中可行性的前提。我们的主要目标是比较儿科黑色素瘤与对照队列中这些 TAA 的表达。在这项回顾性病例对照研究中，使用免疫组织化学染色和数字病理学（QuPath）和逆转录定量 PCR 分析了 25 例儿科黑色素瘤、31 例年轻成人黑色素瘤、29 例成人黑色素瘤和 30 例儿童良性黑色素细胞痣中 NY-ESO-1、酪氨酸酶、MAGE-A3 和 TPTE 的蛋白和转录表达。基于 IHC 分析，儿科黑色素瘤表达酪氨酸酶（100.0%）、TPTE（44.0%）、MAGE-A3（12.0%）和 NY-ESO-1（8.0%）。年轻成人黑色素瘤表达酪氨酸酶（96.8%）、NY-ESO-1（19.4%）、MAGE-A3（19.4%）和 TPTE（3.2%）。成人黑色素瘤表达酪氨酸酶（86.2%）、MAGE-A3（75.9%）、NY-ESO-1（48.3%）和 TPTE（48.3%）。儿童黑色素细胞痣仅表达酪氨酸酶（93.3%）。个体 TAA 的表达流行率在儿科黑色素瘤的亚型之间没有差异，也没有发现与预后相关。所有四个 TAA 都在儿科黑色素瘤中表达，尽管 NY-ESO-1 和 MAGE-A3 的表达程度低于成人黑色素瘤。这些数据支持研究针对这些 TAA 的疫苗治疗儿科黑色素瘤的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/2d17542df206/428_2024_3846_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/c9127880a12a/428_2024_3846_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/3604d7b398ab/428_2024_3846_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/08612b87f1e8/428_2024_3846_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/2d17542df206/428_2024_3846_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/c9127880a12a/428_2024_3846_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/3604d7b398ab/428_2024_3846_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/08612b87f1e8/428_2024_3846_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b0/11329550/2d17542df206/428_2024_3846_Fig4_HTML.jpg

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