Application of mass spectrometry-based MHC immunopeptidome profiling in neoantigen identification for tumor immunotherapy

Abstract

One of the challenges for cancer vaccine and adoptive T-cell-based immunotherapy is to identify the major histocompatibility complex (MHC)-associated non-self neoantigens recognized by T cells. T cell epitope in silico prediction algorithms have been widely used for neoantigen prediction; nonetheless, this platform lacks the experimental evidence of directly identification of the presented epitopes on cell surface. Currently, mass spectrometry (MS)-based proteomics is an advanced analytical technology for large-scale peptide sequencing, which has become a powerful tool for directly profiling the immunopeptidome presented by MHC molecules. Integrating with next-generation sequencing, proteogenomic analysis provides the "gold standard" for neoantigen identification at protein level. This method discovers the tumor-specific neoantigens derived from somatic mutations, proteasome splicing, noncoding RNA, and post-translational modified antigens. Herein, we review basis of antigen processing and presentation, tumor antigen classification, existing approaches for neoantigen discovery, quantitative proteomics, epitope prediction programs, and advantages and drawbacks of proteomics workflow for MHC immunopeptidome profiling. Furthermore, we summarize 40 recently published reports addressing the fundamental theory, breakthrough and most advanced updates for the mass spectrometry-based neoantigen discovery for cancer immunotherapy.

Keywords: Cancer immunotherapy; MHC immunopeptidome; Mass spectrometry-based proteomics; T cell epitope prediction; neoAntigens.