Differential Ion Mobility Mass Spectrometry in Immunopeptidomics Identifies Neoantigens Carrying Colorectal Cancer Driver Mutations

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Aug 18

PMID 35982173

Authors

Yuriko Minegishi

Kazuma Kiyotani

Kensaku Nemoto

Yoshikage Inoue

Yoshimi Haga

Risa Fujii

Naomi Saichi

Satoshi Nagayama

Koji Ueda

Affiliations

Soon will be listed here.

Abstract

Understanding the properties of human leukocyte antigen (HLA) peptides (immunopeptides) is essential for precision cancer medicine, while the direct identification of immunopeptides from small biopsies of clinical tissues by mass spectrometry (MS) is still confronted with technical challenges. Here, to overcome these hindrances, high-field asymmetric waveform ion mobility spectrometry (FAIMS) is introduced to conduct differential ion mobility (DIM)-MS by seamless gas-phase fractionation optimal for scarce samples. By established DIM-MS for immunopeptidomics analysis, on average, 42.9 mg of normal and tumor colorectal tissues from identical patients (n = 17) were analyzed, and on average 4921 immunopeptides were identified. Among these 44,815 unique immunopeptides, two neoantigens, KRAS-G12V and CPPED1-R228Q, were identified. These neoantigens were confirmed by synthetic peptides through targeted MS in parallel reaction monitoring (PRM) mode. Comparison of the tissue-based personal immunopeptidome revealed tumor-specific processing of immunopeptides. Since the direct identification of neoantigens from tumor tissues suggested that more potential neoantigens have yet to be identified, we screened cell lines with known oncogenic KRAS mutations and identified 2 more neoantigens that carry KRAS-G12V. These results indicated that the established FAIMS-assisted DIM-MS is effective in the identification of immunopeptides and potential recurrent neoantigens directly from scarce samples such as clinical tissues.

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