Nine Human Leukocyte Antigen (HLA) Class I Alleles are Omnipotent Against 11 Antigens Expressed in Melanoma Tumors.

IF 2.4 Q2 MATHEMATICAL & COMPUTATIONAL BIOLOGY Cancer Informatics Pub Date : 2024-08-27 eCollection Date: 2024-01-01 DOI:10.1177/11769351241274160

Apostolos P Georgopoulos, Lisa M James, Matthew Sanders

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Abstract

Objective: Host immunogenetics (Human Leukocyte Antigen, HLA) play a critical role in the human immune response to melanoma, influencing both melanoma prevalence and immunotherapy outcomes. Beneficial outcomes hinge on the successful binding of epitopes of melanoma antigens to HLA Class I molecules for an effective engagement of cytotoxic CD8+ lymphocytes and subsequent elimination of the cancerous cell. This study evaluated the binding affinity and immunogenicity of HLA Class I to melanoma tumor antigens to identify alleles best suited to facilitate elimination of melanoma antigens.

Methods: In this study, we used freely available software tools to determine in silico the binding affinity and immunogenicity of 2462 reported HLA Class I alleles to all linear nonamer epitopes of 11 known antigens expressed in melanoma tumors (TRP2, S100, Tyrosinase, TRP1, PMEL(17), MAGE1, MAGE4, CTA, BAGE, GAGE/SSX2, Melan).

Results: We identified the following 9 HLA Class I alleles with very high immunogenicity and binding affinity against all 11 melanoma antigens: A*02:14, B*07:10, B*35:10, B*40:10, B*40:12, B*44:10, C*07:11, and C*07:13, and C*07:14.

Conclusion: These 9 HLA alleles possess the potential to aid in the elimination of melanoma both by themselves and by enhancing the beneficial effect of immune checkpoint inhibitors.

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九种人类白细胞抗原 (HLA) I 类等位基因对黑色素瘤肿瘤中表达的 11 种抗原具有全能性。

目的：宿主免疫遗传学（人类白细胞抗原，HLA）在人类对黑色素瘤的免疫反应中起着至关重要的作用，影响着黑色素瘤的发病率和免疫疗法的效果。疗效取决于黑色素瘤抗原表位与 HLA I 类分子的成功结合，从而使细胞毒性 CD8+ 淋巴细胞有效参与并随后消灭癌细胞。本研究评估了HLA I类分子与黑色素瘤肿瘤抗原的结合亲和力和免疫原性，以确定最适合促进消除黑色素瘤抗原的等位基因：在这项研究中，我们使用可免费获得的软件工具，对已报道的2462个HLA I类等位基因与黑色素瘤肿瘤中表达的11种已知抗原（TRP2、S100、酪氨酸酶、TRP1、PMEL(17)、MAGE1、MAGE4、CTA、BAGE、GAGE/SSX2、Melan）的所有线性非等位基因表位的结合亲和力和免疫原性进行了硅学测定：我们确定了以下 9 个 HLA I 类等位基因，它们对所有 11 种黑色素瘤抗原具有极高的免疫原性和结合亲和力：A*02:14、B*07:10、B*35:10、B*40:10、B*40:12、B*44:10、C*07:11、C*07:13 和 C*07:14：这 9 个 HLA 等位基因本身就有可能帮助消除黑色素瘤，而且还能增强免疫检查点抑制剂的有益效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Informatics Medicine-Oncology

CiteScore

3.00

自引率

5.00%

发文量

审稿时长

8 weeks

期刊介绍： The field of cancer research relies on advances in many other disciplines, including omics technology, mass spectrometry, radio imaging, computer science, and biostatistics. Cancer Informatics provides open access to peer-reviewed high-quality manuscripts reporting bioinformatics analysis of molecular genetics and/or clinical data pertaining to cancer, emphasizing the use of machine learning, artificial intelligence, statistical algorithms, advanced imaging techniques, data visualization, and high-throughput technologies. As the leading journal dedicated exclusively to the report of the use of computational methods in cancer research and practice, Cancer Informatics leverages methodological improvements in systems biology, genomics, proteomics, metabolomics, and molecular biochemistry into the fields of cancer detection, treatment, classification, risk-prediction, prevention, outcome, and modeling.