Given the emerging importance of mutation-derived neoepitopes in cancer immunotherapy, Smart and Margolis et al. developed a computational approach to examine tumor cells for aberrant RNA splicing leading to translationally in-frame retained introns (RI). After eliminating sources of artifact, binding predictions indicated that RI from dysregulated splicing led to as many HLA-restricted neoepitopes as non-synonymous mutations, and several of these could be observed as presented peptides by mass spectrometry. Although further validation is required, this could represent an important new source of personalized immune targets.
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.
Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. (2) Department of M
Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. (2) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. (3) Department of Genetics and Biology, Stanford University, Stanford, California, USA. (4) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. (5) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. (6) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York, USA. (7) Philochem AG, Otelfingen, Switzerland. (8) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York, USA. (9) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
