Pluto Bioinformatics

GSE111092: Non-coding regions are the main source of tumor-specific antigens [mouse]

Bulk RNA sequencing

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 two murine cell lines, namely EL4 and CT26 cells.; Methods: We performed RNA-Sequencing on both tumor cell lines (unreplicated) as well as on the syngeneic mature medullary thymic epithelial cells (mTEChi, in triplicate), using either the Illumina HiSeq200 or the Illumina NextSeq 500. Using those RNA-Sequencing data to build a global cancer database for each tumor cell line, we performed a transcriptomic-informed mass spectrometry analysis of their MHC I-associated peptides to identify TSAs.; Results: We identified a total of 21 TSAs, 90% of which derived from allegedly non-coding regions and would have been missed by standard approaches. Moreover, about 70% of these TSAs derived from non-mutated yet cancer-restricted transcripts (e.g., endogenous retroelements) 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. SOURCE: Krystel Vincent (krystel.vincent.1@gmail.com) - Immunobiology - Claude Perreault Institute for Research in Immunology and Cancer