TOF mass spectrometry-based immunopeptidomics refines tumor antigen identification.

Publication

TOF mass spectrometry-based immunopeptidomics refines tumor antigen identification.

Journal Paper/Review - Nov 17, 2023

Hoenisch Gravel Naomi, Nelde Annika, Bauer Jens, Mühlenbruch Lena, Schroeder Sarah M, Neidert Marian Christoph, Scheid Jonas, Lemke Steffen, Dubbelaar MariLisa, Wacker Marcel, Dengler Anna, Klein Reinhild, Mauz Paul-Stefan, Löwenheim Hubert, Hauri-Hohl Mathias, Martin Roland, Hennenlotter Jörg, Stenzl Arnulf, Heitmann Jonas S, Salih Helmut Rainer, Rammensee Hans-Georg, Walz Juliane Sarah

Citation

Hoenisch Gravel N, Nelde A, Bauer J, Mühlenbruch L, Schroeder S, Neidert M, Scheid J, Lemke S, Dubbelaar M, Wacker M, Dengler A, Klein R, Mauz P, Löwenheim H, Hauri-Hohl M, Martin R, Hennenlotter J, Stenzl A, Heitmann J, Salih H, Rammensee H, Walz J. TOF mass spectrometry-based immunopeptidomics refines tumor antigen identification. Nat Commun 2023; 14:7472.

Type

Journal Paper/Review (English)

Journal

Nat Commun 2023; 14

Publication Date

Nov 17, 2023

Issn Electronic

2041-1723

Pages

7472

Brief description/objective

T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the implementation of ion mobility separation-based time-of-flight (TOF) MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. Applying TOF-based immunopeptidomics, a novel extensive benign dataset was generated from 94 primary benign samples of solid tissue and hematological origin, which enabled the expansion of benign reference immunopeptidome databases with > 150,000 HLA-presented peptides, the refinement of previously described tumor antigens, as well as the identification of frequently presented self antigens and not yet described tumor antigens comprising low abundant mutation-derived neoepitopes that might serve as targets for future cancer immunotherapy development.