Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry
Open accessAbstract
Although mutations may represent attractive targets for immunotherapy, direct identification of mutated peptide ligands isolated from human leucocyte antigens (HLA) on the surface of native tumour tissue has so far not been successful. Using advanced mass spectrometry (MS) analysis, we survey the melanoma-associated immunopeptidome to a depth of 95,500 patient-presented peptides. We thereby discover a large spectrum of attractive target antigen candidates including cancer testis antigens and phosphopeptides. Most importantly, we identify peptide ligands presented on native tumour tissue samples harbouring somatic mutations. Four of eleven mutated ligands prove to be immunogenic by neoantigen-specific T-cell responses. Moreover, tumour-reactive T cells with specificity for selected neoantigens identified by MS are detected in the patient’s tumour and peripheral blood. We conclude that direct identification of mutated peptide ligands from primary tumour material by MS is possible and yields true neoepitopes with high relevance for immunotherapeutic strategies in cancer.
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- Authors
- Bassani-Sternberg, M., Bräunlein, E., Klar, R., Engleitner, T., Sinitcyn, P., Audehm, S., Straub, M., Weber, J., Slotta-Huspenina, J., Specht, K., Martignoni, M. E., Werner, A., Hein, R., H. Busch, D., Peschel, C., Rad, R., Cox, J., Mann, M., & Krackhardt, A. M.
- Affiliations
- TUM Klinikum (DE)
- German Cancer Research Center (DE)
- Max Planck Institute of Biochemistry (DE)
- Technical University of Munich (DE)
- Corresponding author
- Mann, Matthias
- Krackhardt, Angela M.
- ORCID
- Venue
- Nature Communications
- Published
- 2016-11-21
- Volume
- 7
- Issue
- 1
- Pages
- 13404-13404
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5121339
- OpenAlex
- W2555228033
- Cited by
- 693
- References
- 6
- Citations by year
- 2026: 69 · 2025: 56 · 2024: 51 · 2023: 77 · 2022: 67 · 2021: 85 · 2020: 89 · 2019: 81 · 2018: 67 · 2017: 50
- FWCI
- 30.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by)
- IRIS (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- Wilhelm Sander-Stiftung (2015.030.1)
- Deutsche Forschungsgemeinschaft (SFB824)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- melanoma, neoantigens, immunopeptidome, HLA-presented peptides, somatic mutations, cancer-testis antigens, phosphopeptides, cancer immunotherapy, tumor tissue
- MeSH terms
- Epitopes, Antigens, Neoplasm, Base Sequence, Cloning, Molecular, Humans, Ligands, Melanoma, Mutation, Peptides, Mass Spectrometry, Gene Expression Regulation, Neoplastic, Antigen Presentation
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