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

Details

Serval ID
serval:BIB_7CEBBFB3FC0C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry.
Journal
Nature communications
Author(s)
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.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
21/11/2016
Peer-reviewed
Oui
Volume
7
Pages
13404
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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.
Keywords
Antigen Presentation, Antigens, Neoplasm, Base Sequence, Cloning, Molecular, Epitopes/genetics, Epitopes/metabolism, Gene Expression Regulation, Neoplastic, Humans, Ligands, Mass Spectrometry, Melanoma/immunology, Melanoma/metabolism, Mutation, Peptides/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
26/07/2019 16:11
Last modification date
10/10/2020 5:21
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