Bedran, Georges;
Gasser, Hans-Christof;
Weke, Kenneth;
Wang, Tongjie;
Bedran, Dominika;
Laird, Alexander;
Battail, Christophe;
... Alfaro, Javier A; + view all
(2023)
The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides.
Cancer Immunology Research
, 11
(6)
pp. 747-762.
10.1158/2326-6066.CIR-22-0621.
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Abstract
Tumor antigens can emerge through multiple mechanisms, including translation of non-coding genomic regions. This non-canonical category of antigens has recently gained attention; however, our understanding of how they recur within and between cancer types is still in its infancy. Therefore, we developed a proteogenomic pipeline based on deep learning de novo mass spectrometry to enable the discovery of non-canonical MHC-associated peptides (ncMAPs) from non-coding regions. Considering that the emergence of tumor antigens can also involve post-translational modifications, we included an open search component in our pipeline. Leveraging the wealth of mass spectrometry-based immunopeptidomics, we analyzed 26 MHC class I immunopeptidomic studies of 9 different cancer types. We validated the de novo identified ncMAPs, along with the most abundant post-translational modifications, using spectral matching and controlled their false discovery rate (FDR) to 1%. Interestingly, the non-canonical presentation appeared to be 5 times enriched for the A03 HLA supertype, with a projected population coverage of 54.85%. Here, we reveal an atlas of 8,601 ncMAPs with varying levels of cancer selectivity and suggest 17 cancer-selective ncMAPs as attractive targets according to a stringent cutoff. In summary, the combination of the open-source pipeline and the atlas of ncMAPs reported herein could facilitate the identification and screening of ncMAPs as targeting agents for T-cell therapies or vaccine development.
| Type: | Article |
|---|---|
| Title: | The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1158/2326-6066.CIR-22-0621 |
| Publisher version: | http://doi.org/10.1158/2326-6066.CIR-22-0621 |
| Language: | English |
| Additional information: | © 2023 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10169879 |
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