Intron retention is a source of neoepitopes in cancer

• Published in: Nature biotechnology Vol. 36; no. 11; pp. 1056 - 1058
• Main Authors: Smart, Alicia C, Margolis, Claire A, Pimentel, Harold, He, Meng Xiao, Miao, Diana, Adeegbe, Dennis, Fugmann, Tim, Wong, Kwok-Kin, Van Allen, Eliezer M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2018; Nature Publishing Group
• Subjects: 38/91; 49/39; 631/114; 631/208/1792; 631/250/21; 631/250/590/2030; 631/67/580; 82/58; Agriculture; Analysis; Antigenic determinants; Antigens; Bioinformatics; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; brief-communication; Cancer; Cancer vaccines; Cancer Vaccines - immunology; Cell cycle; Cell Line, Tumor; Computer Simulation; DNA damage; Epitope Mapping; Epitopes - genetics; Epitopes - metabolism; Gene expression; Genes; Genetic aspects; Humans; Immunotherapy; Introns; Introns - genetics; Ipilimumab; Life Sciences; Major histocompatibility complex; Mass spectrometry; Mass spectroscopy; Medical centers; Melanoma; Models, Genetic; Mutation; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - therapy; Patients; Peptides; Retention; Ribonucleic acid; RNA; RNA - genetics; RNA sequencing; Scientific imaging; Spectroscopy; Transcription (Genetics); Transcriptomes; Tumor cell lines; Tumors; Vaccine development; Vaccines
• ISSN: 1087-0156; 1546-1696; 1546-1696
• DOI: 10.1038/nbt.4239

Neoepitopes derived from intron retention events are processed and presented on MHC I in cancer cell lines. We present an in silico approach to identifying neoepitopes derived from intron retention events in tumor transcriptomes. Using mass spectrometry immunopeptidome analysis, we show that retained intron neoepitopes are processed and presented on MHC I on the surface of cancer cell lines. RNA-derived neoepitopes should be considered for prospective personalized cancer vaccine development.