Proteogenomic analysis reveals RNA as an important source for tumor-agnostic neoantigen identification
Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types by combining proteogenomics with phenotypic and functional analyses. By using an optimized computational approach, we discovered a large number of novel tumor-specific and tumor-associated antigens including shared common target candidates. To create a pipeline for the identification of neoantigens in our cohort, we combined deep DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity. In fact, we could detect a broad variety of non-wild type HLA-binding peptides in the majority of patients and confirmed the immunogenicity of 24 neoantigens. Most interestingly, the majority of total and immunogenic neoantigens originated from variants identified in the RNA dataset, illustrating the importance of RNA as a still understudied source of cancer antigens. Moreover, the amount of these mainly RNA-based immunogenic neoantigens correlated positively with overall CD8+ tumor-infiltrating T cells. This study therefore underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.  The data associated with the study ID PRJEB61429, that is part of the paper "Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification" (https://doi.org/10.1038/s41467-023-39570-7), was moved to the European Genome-phenome Archive (EGA). The data can then be found on EGA with the study identifier EGAS00001006706 (https://ega-archive.org/studies/EGAS00001006706) and the dataset identifier EGAD50000000193 along with the other datasets that are part of the paper.