Identification of shared neoantigens in esophageal carcinoma by the combination of comprehensive analysis of genomic data and in silico neoantigen prediction

Abstract

Neoantigens are attractive targets for cancer immunotherapy. The identification of neoantigens shared by different patients could promote the broad application of neoantigen-based immunotherapy. This study aimed to investigate shared neoantigens in esophageal carcinoma. By combining a comprehensive analysis of mutation data of 722 patients with esophageal carcinoma (EC) and in silico neoantigen prediction, we obtained 216 recurrent neoantigen candidates predicted to bind to high-frequency class I human leukocyte antigen (HLA) alleles. We further performed immunogenicity validation tests on five high-frequency HLA-A*0201 binding neoantigens derived from TP53 mutations. The results demonstrated that the peptides p53 H193R_{193_203}, R248Q_{245_254}, and R273H_{264_274} could efficiently prime peptide-specific CD8⁺ T cells to secrete IFN-γ and lyse mutant peptide-pulsed T2 cells. In conclusion, we obtained a group of shared neoantigen candidates in esophageal carcinoma and validated the immunogenicity of three novel TP53 neoantigens. These peptides might be potential targets for immunotherapy.

Keywords: Comprehensive analysis; Esophageal carcinoma; Immunotherapy; Recurrent mutation; Shared neoantigen.