Details

Autor(en) / Beteiligte

• Chong, Chloe
• Müller, Markus
• Pak, HuiSong
• Harnett, Dermot
• Huber, Florian
• Grun, Delphine
• Leleu, Marion
• Auger, Aymeric
• Arnaud, Marion
• Stevenson, Brian J.
• Michaux, Justine
• Bilic, Ilija
• Hirsekorn, Antje
• Calviello, Lorenzo
• Simó-Riudalbas, Laia
• Planet, Evarist
• Lubiński, Jan
• Bryśkiewicz, Marta
• Wiznerowicz, Maciej
• Xenarios, Ioannis
• Zhang, Lin
• Trono, Didier
• Harari, Alexandre
• Ohler, Uwe
• Coukos, George
• Bassani-Sternberg, Michal

Titel

Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes

Ist Teil von

• Nature communications, 2020-03, Vol.11 (1), p.1293-1293, Article 1293

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides derived from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass spectrometry (MS)-based proteogenomics approaches are required to robustly identify these non-canonical peptides. We present an MS-based analytical approach that characterizes the non-canonical tumor HLA peptide repertoire, by incorporating whole exome sequencing, bulk and single-cell transcriptomics, ribosome profiling, and two MS/MS search tools in combination. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLA peptides, including an immunogenic peptide derived from an open reading frame downstream of the melanoma stem cell marker gene ABCB5 . These findings hold great promise for the discovery of previously unknown tumor antigens for cancer immunotherapy. Non-canonical HLA-bound peptides from presumed non-coding regions are potential targets for cancer immunotherapy, but their discovery remains challenging. Here, the authors integrate exome sequencing, transcriptomics, ribosome profiling, and immunopeptidomics to identify tumor-specific non-canonical HLA-bound peptides.