Melanoma and Human Leukocyte Antigen (HLA): Immunogenicity of 69 HLA Class I Alleles With 11 Antigens Expressed in Melanoma Tumors

Apostolos P Georgopoulos; Lisa M James; Spyros A Charonis; Matthew Sanders

doi:10.1177/11769351231172604

Melanoma and Human Leukocyte Antigen (HLA): Immunogenicity of 69 HLA Class I Alleles With 11 Antigens Expressed in Melanoma Tumors

Cancer Inform. 2023 May 22:22:11769351231172604. doi: 10.1177/11769351231172604. eCollection 2023.

Authors

Apostolos P Georgopoulos^{1

2

3

4}, Lisa M James^{1

2

3}, Spyros A Charonis^{1

2}, Matthew Sanders^{1

2}

Affiliations

¹ The HLA Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA.
² Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA.
³ Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA.
⁴ Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.

Abstract

Host immunogenetics play a critical role in the human immune response to melanoma, influencing both melanoma prevalence and immunotherapy outcomes. Beneficial outcomes that stimulate T cell response hinge on binding affinity and immunogenicity of human leukocyte antigen (HLA) with melanoma antigen epitopes. Here, we use an in silico approach to characterize binding affinity and immunogenicity of 69 HLA Class I human leukocyte antigen alleles to epitopes of 11 known melanoma antigens. The findings document a significant proportion of positively immunogenic epitope-allele combinations, with the highest proportions of positive immunogenicity found for the Q13072/BAGE1 melanoma antigen and alleles of the HLA B and C genes. The findings are discussed in terms of a personalized precision HLA-mediated adjunct to immune checkpoint blockade immunotherapy to maximize tumor elimination.

Keywords: Melanoma; human leukocyte antigen; immunogenicity; major histocompatibility complex; neoantigens.