{
  "abstract": "Background/ObjectivesCancer immunotherapy predominantly targets mutation-derived neoantigens, thereby limiting its efficacy in low-mutational-burden tumours such as pancreatic and paediatric cancers. Non-canonical open reading frames (ncORFs) generate a diverse repertoire of peptides, the dark immunopeptidome, including upstream ORFs, lncRNA-derived ORFs, and transposable element-derived ORFs, which are efficiently presented by MHC class I molecules.MethodsA narrative synthesis of peer-reviewed literature integrating ribosome profiling, immunopeptidomics, proteogenomics, and functional T-cell assays was conducted across multiple tumour types.ResultsEvidence demonstrates that ncORF-derived peptides are frequently tumour-enriched at the transcript or translation level, and a proportion has been directly identified at the peptide level by HLA-elution immunopeptidomics from primary tumour tissue; a subset can prime antigen-specific CD8+ T-cell responses ex vivo, with cytotoxic activity demonstrated against peptide-pulsed targets in vitro and, in selected cases, against endogenously processed tumour cells. These ncORF-derived antigens may partially evade, and direct human thymic immunopeptidome data are lacking.ConclusionsIncorporating ncORF-derived antigens into personalised cancer vaccine strategies could expand therapeutic targets, especially for low-mutational burden and therapy-resistant tumours, but requires further bioinformatic refinement and rigorous safety validation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "name": "Ivo Fierro-Monti"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/822xfr4mr50ae.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1939091",
  "fulltext_url": null,
  "id": "822xfr4mr50ae",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1939091",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/822xfr4mr50ae.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:20:19Z",
      "native_id": "10.3389/fimmu.2026.1939091",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1939091"
    },
    {
      "first_seen": "2026-11-03T12:21:20Z",
      "native_id": "10.3389/fimmu.2026.1939091",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1939091/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Non-canonical open reading frame-derived antigens as emerging immune targets in cancer immunotherapy",
  "title_text": "Non-canonical open reading frame-derived antigens as emerging immune targets in cancer immunotherapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:21:02Z",
  "url": "https://research.draconitic.com/paper/822xfr4mr50ae",
  "venue": "Frontiers in Immunology",
  "versions": []
}