ArticleNature cancer2021
Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- HLA-II peptide-binding diversity shapes humoral immune responses and susceptibility to infections.Nature communications · 2026Article
- Five dominant amino acid substitution signatures shape tumour immunity.Molecular systems biology · 2026Article
- CAR-T therapy-based innovations in the enhancement of contemporary anti-tumor therapies.Frontiers in immunology · 2025Review
- Review
- A journey to your self: The vague definition of immune self and its practical implications.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A spatial architecture-embedding HLA signature to predict clinical response to immunotherapy in renal cell carcinoma.Nature medicine · 2024Article
- Heritable and spatial immunogenic traits co-predict the efficacy of immunotherapy in kidney cancer.Nature medicine · 2024Article
- The HLA-I landscape confers prognosis and antitumor immunity in breast cancer.Briefings in bioinformatics · 2024Review
- Historical perspective and future directions: computational science in immuno-oncology.Journal for immunotherapy of cancer · 2024Review
- Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity.bioRxiv : the preprint server for biology · 2023Article
- Determinants of tumor immune evasion: the role of T cell exposed motif frequency and mutant amino acid exposure.Frontiers in immunology · 2023Article
- 'Know thyself' - host factors influencing cancer response to immune checkpoint inhibitors.The Journal of pathology · 2022Review
- HLA-I-restricted CD8iScience · 2022Article
- HLA Class I Downregulation in Progressing Metastases of Melanoma Patients Treated With Ipilimumab.Pathology oncology research : POR · 2022Article
- Computational cancer neoantigen prediction: current status and recent advances.Immuno-oncology technology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human leukocyte antigen class I (HLA-I) genes shape our immune response against pathogens and cancer. Certain HLA-I variants can bind a wider range of peptides than others, a feature that could be favorable against a range of viral diseases. However, the implications of this phenomenon on cancer immune response are unknown. Here we quantified peptide repertoire breadth (or promiscuity) of a representative set of HLA-I alleles and found that patients with cancer who were carrying HLA-I alleles with high peptide-binding promiscuity have significantly worse prognosis after immune checkpoint inhibition. This can be explained by a reduced capacity of the immune system to discriminate tumor neopeptides from self-peptides when patients carry highly promiscuous HLA-I variants, shifting the regulation of tumor-infiltrating T cells from activation to tolerance. In summary, HLA-I peptide-binding specificity shapes neopeptide immunogenicity and the self-immunopeptidome repertoire in an antagonistic manner, and could underlie a negative trade-off between antitumor immunity and genetic susceptibility to viral infections.
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Registered trials
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