Patient-specific HLA-I subtypes predict response to immune checkpoint blockade

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 adv...

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Main Authors: Kyrillus S. Shohdy, Jack Atherton, Jessica Longland, Jennifer Alison, Manon Pillai, Fiona Thistlethwaite
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2462386
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author Kyrillus S. Shohdy
Jack Atherton
Jessica Longland
Jennifer Alison
Manon Pillai
Fiona Thistlethwaite
author_facet Kyrillus S. Shohdy
Jack Atherton
Jessica Longland
Jennifer Alison
Manon Pillai
Fiona Thistlethwaite
author_sort Kyrillus S. Shohdy
collection DOAJ
description 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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spelling doaj-art-cf36b4aee176463da8b58fc0051d28cb2025-08-20T03:48:27ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2462386Patient-specific HLA-I subtypes predict response to immune checkpoint blockadeKyrillus S. Shohdy0Jack Atherton1Jessica Longland2Jennifer Alison3Manon Pillai4Fiona Thistlethwaite5Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UKExperimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UKExperimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UKExperimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UKExperimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UKExperimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UKSpecific 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.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2462386Advanced cancerHLA subtypeimmune checkpointpredictive biomarkers
spellingShingle Kyrillus S. Shohdy
Jack Atherton
Jessica Longland
Jennifer Alison
Manon Pillai
Fiona Thistlethwaite
Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
OncoImmunology
Advanced cancer
HLA subtype
immune checkpoint
predictive biomarkers
title Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
title_full Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
title_fullStr Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
title_full_unstemmed Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
title_short Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
title_sort patient specific hla i subtypes predict response to immune checkpoint blockade
topic Advanced cancer
HLA subtype
immune checkpoint
predictive biomarkers
url https://www.tandfonline.com/doi/10.1080/2162402X.2025.2462386
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