Non-coding regions are the main source of tumor-specific antigens [human]. Non-coding regions are the main source of tumor-specific antigens [human]

Purpose: Tumor-specific antigens (TSAs) represent ideal targets for cancer immunotherapy, but very few of them have been identified. Therefore, the goal of this study was to develop a novel approach, combining RNA-Sequencing and mass spectrometry, to enlarge the landscape of actionable TSAs in seven human primary samples, namely 4 B-ALL and 3 lung tumor biopsies. Methods: We performed RNA-Sequencing on each primary tumor sample (unreplicated) with the Illumina HiSeq2000. Using those RNA-Sequencing data to build a global cancer database for each sample, we performed a transcriptomic-informed mass spectrometry analysis of their MHC I-associated peptides to identify TSAs. Results: We identified a total of 30 TSAs, 90% of which derived from allegedly non-coding regions and would have been missed by standard approaches. Moreover, most of these TSAs derived from non-mutated yet cancer-restricted transcripts that can be shared by multiple tumors. Conclusions: In conclusion, the strategy reported herein is readily applicable to human tumors and should considerably enlarge the landscape of actionable TSAs. Overall design: Transcriptomic analysis of 7 human primary tumor samples using the Illumina HiSeq 2000.