Transposable Element neo-Antigens in CAncer – TEA-CA

Transposable elements (TEs) are DNA sequences capable of moving within the genome and represent nearly 50% of the human genome compared to only 3 to 4% for protein-coding genes. In cancer, TEs are hypomethylated and it has been shown that some of them can encode peptides that are presented by HLA class I molecules. In this project, we propose to identify, using a proteo-genomic approach, TEs encoding antigenic peptides in different tumor types selected based on their mutation rate and identifying whether the peptides are shared or specific to a tumor type. Thus, we propose to analyze (i) the expression of TEs at the transcriptomic scale using data sequenced in bulk or at the single cell scale, (ii) to identify by immunopeptidomics TE derived peptides, (iii) to detect specific T lymphocyte clones in patients of a given peptide by using tetramers in flow cytometry and (iv) to develop an algorithm for predicting the immunogenicity of peptides derived from TEs. Our results will contribute to a better understanding of the role of TEs in cancer and identification of new therapeutic targets in immunotherapy.