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  Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry

Bassani-Sternberg, M., Braunlein, E., Klar, R., Engleitner, T., Sinitcyn, P., Audehm, S., et al. (2016). Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nature Communications, 7: 13404. doi:10.1038/ncomms13404.

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Bassani-Sternberg, Michal1, Author              
Braunlein, Eva2, Author
Klar, Richard2, Author
Engleitner, Thomas2, Author
Sinitcyn, Pavel1, Author              
Audehm, Stefan2, Author
Straub, Melanie2, Author
Weber, Julia2, Author
Slotta-Huspenina, Julia2, Author
Specht, Katja2, Author
Martignoni, Marc E.2, Author
Werner, Angelika2, Author
Hein, Rudiger2, Author
Busch, Dirk H.2, Author
Peschel, Christian2, Author
Rad, Roland2, Author
Cox, Jürgen3, Author              
Mann, Matthias1, Author              
Krackhardt, Angela M.2, Author
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              
3Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_2063284              

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Free keywords: MHC CLASS-I; T-CELL RESPONSES; PERIPHERAL-BLOOD; CTLA-4 BLOCKADE; CANCER; TUMOR; ANTIGENS; LYMPHOCYTES; REACTIVITY; REVEALSScience & Technology - Other Topics;
 Abstract: 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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Language(s): eng - English
 Dates: 2016-11-21
 Publication Status: Published online
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000388078700001
DOI: 10.1038/ncomms13404
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 7 Sequence Number: 13404 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723