Potential shared neoantigens from pan-cancer transcript isoforms

Abstract Isoform switching in cancer is a prevalent phenomenon with significant implications for immunotherapy, as actionable neoantigens derived from these cancer-specific events would be applicable to broad categories of patients, reducing the necessity for personalized treatments. By integrating...

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Main Authors: Jirapat Techachakrit, Aijaz Ahmad Malik, Trairak Pisitkun, Sira Sriswasdi
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-00817-6
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author Jirapat Techachakrit
Aijaz Ahmad Malik
Trairak Pisitkun
Sira Sriswasdi
author_facet Jirapat Techachakrit
Aijaz Ahmad Malik
Trairak Pisitkun
Sira Sriswasdi
author_sort Jirapat Techachakrit
collection DOAJ
description Abstract Isoform switching in cancer is a prevalent phenomenon with significant implications for immunotherapy, as actionable neoantigens derived from these cancer-specific events would be applicable to broad categories of patients, reducing the necessity for personalized treatments. By integrating five large-scale transcriptomic datasets comprising over 19,500 samples across 29 cancer and 54 normal tissue types, we identified cancer-associated isoform switching events common to multiple cancer types, several of which involve genes with established mechanistic roles in oncogenesis. The presence of neoantigen-containing peptides derived from these transcripts was confirmed in broad cancer and normal tissue proteome datasets and the binding affinity of predicted neoantigens to the human leukocyte antigen (HLA) complex via molecular dynamics simulations. The study presents strong evidence that isoform switching in cancer is a significant source of actionable neoantigens that have the capability to trigger an immune response. These findings suggest that isoform switching events could potentially be leveraged for broad immunotherapeutic strategies across various cancer types.
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spelling doaj-art-b07e76142167415dabc458d00d7e74902025-08-20T03:53:12ZengNature PortfolioScientific Reports2045-23222025-05-0115111510.1038/s41598-025-00817-6Potential shared neoantigens from pan-cancer transcript isoformsJirapat Techachakrit0Aijaz Ahmad Malik1Trairak Pisitkun2Sira Sriswasdi3Center of Excellence in Computational Molecular Biology, Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Computational Molecular Biology, Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Computational Molecular Biology, Faculty of Medicine, Chulalongkorn UniversityAbstract Isoform switching in cancer is a prevalent phenomenon with significant implications for immunotherapy, as actionable neoantigens derived from these cancer-specific events would be applicable to broad categories of patients, reducing the necessity for personalized treatments. By integrating five large-scale transcriptomic datasets comprising over 19,500 samples across 29 cancer and 54 normal tissue types, we identified cancer-associated isoform switching events common to multiple cancer types, several of which involve genes with established mechanistic roles in oncogenesis. The presence of neoantigen-containing peptides derived from these transcripts was confirmed in broad cancer and normal tissue proteome datasets and the binding affinity of predicted neoantigens to the human leukocyte antigen (HLA) complex via molecular dynamics simulations. The study presents strong evidence that isoform switching in cancer is a significant source of actionable neoantigens that have the capability to trigger an immune response. These findings suggest that isoform switching events could potentially be leveraged for broad immunotherapeutic strategies across various cancer types.https://doi.org/10.1038/s41598-025-00817-6Shared pan-cancer neoantigensIsoform switchingImmunotherapy targets
spellingShingle Jirapat Techachakrit
Aijaz Ahmad Malik
Trairak Pisitkun
Sira Sriswasdi
Potential shared neoantigens from pan-cancer transcript isoforms
Scientific Reports
Shared pan-cancer neoantigens
Isoform switching
Immunotherapy targets
title Potential shared neoantigens from pan-cancer transcript isoforms
title_full Potential shared neoantigens from pan-cancer transcript isoforms
title_fullStr Potential shared neoantigens from pan-cancer transcript isoforms
title_full_unstemmed Potential shared neoantigens from pan-cancer transcript isoforms
title_short Potential shared neoantigens from pan-cancer transcript isoforms
title_sort potential shared neoantigens from pan cancer transcript isoforms
topic Shared pan-cancer neoantigens
Isoform switching
Immunotherapy targets
url https://doi.org/10.1038/s41598-025-00817-6
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