Subcellular location of source proteins improves prediction of neoantigens for immunotherapy
Abstract: Antigen presentation via the major histocompatibility complex (MHC) is essential for anti‐tumor immunity. However, the rules that determine which tumor‐derived peptides will be immunogenic are still incompletely understood. Here, we investigated whether constraints on peptide accessibility to the MHC due to protein subcellular location are associated with peptide immunogenicity potential. Analyzing over 380,000 peptides from studies of MHC presentation and peptide immunogenicity, we find clear spatial biases in both eluted and immunogenic peptides. We find that including parent protein location improves the prediction of peptide immunogenicity in multiple datasets. In human immunotherapy cohorts, the location was associated with a neoantigen vaccination response, and immune checkpoint blockade responders generally had a higher burden of neopeptides from accessible locations. We conclude that protein subcellular location adds important information for optimizing cancer immunotherapies.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Subcellular location of source proteins improves prediction of neoantigens for immunotherapy ; day:31 ; month:10 ; year:2022 ; extent:13
The EMBO journal / European Molecular Biology Organization ; (31.10.2022) (gesamt 13)
- Creator
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Castro, Andrea
Kaabinejadian, Saghar
Yari, Hooman
Hildebrand, William
Zanetti, Maurizio
Carter, Hannah
- DOI
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10.15252/embj.2022111071
- URN
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urn:nbn:de:101:1-2022103114363764735981
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:31 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Castro, Andrea
- Kaabinejadian, Saghar
- Yari, Hooman
- Hildebrand, William
- Zanetti, Maurizio
- Carter, Hannah
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