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Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
Shohdy, K. S. Atherton, J. Longland, J. Alison, J. Pillai, M. Thistlethwaite, F.
Shohdy, K. S.
Atherton, J.
Longland, J.
Alison, J.
Pillai, M.
Thistlethwaite, F.
Abstract
Specific shared HLA-I alleles were linked to the response to immune checkpoint blockade (ICB). We aimed to identify the HLA-A subtypes associated with maximum benefit from ICB. We compiled a clinical dataset of patients who underwent a CLIA-approved germline HLA status testing as part of various advanced immune and cell therapy trials undertaken at the Christie NHS Foundation Trust. A total of 285 patients were eligible for final analysis. We identified 15 HLA-A subtypes, the most common alleles being HLA-A02, HLA-A01, and HLA-A03. A02:01 showed a tumor lineage-specific distribution. One hundred and forty patients received ICB and had evaluable response status. Patients with A01 were associated with better clinical outcomes. No significant associations were observed between HLA-A subtypes and the incidence of immune-related adverse effects. HLA genotyping should be incorporated early in the diagnostic work-up of patients with solid cancers as a predictive and selective biomarker.
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Date
2025
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Shohdy KS, Atherton J, Longland J, Alison J, Pillai M, Thistlethwaite F. Patient-specific HLA-I subtypes predict response to immune checkpoint blockade. Oncoimmunology. 2025 Dec;14(1):2462386. PubMed PMID: 39981665. Pubmed Central PMCID: PMC11849918. Epub 2025/02/21. eng.