Transposable elements in GLIOBLASTOMA

Transposable elements (TE) populate 45% of the genome and they are generally overexpressed in cancer due to epigenetic disregulations. We identified that 2 subpopulations of TEs are enriched in glioblastoma immunopeptidome. First, young TEs (mainly LINEs) that share homology with many other transposed copies in the genome, being then redundant and less tumor-specific. A second class of evolutionary older TEs, with mutated and degenerated sequences, was more tumor-enriched and potentially more immunogenic. 

splicing between exons and transposable elements

Aberrant splicing is known to be upregulated in tumors. We then investigated if there are tumor-specific splicing junctions between exons and transposable elements (JETs) in LUAD tumors. We found a population of shared JETs that was translated and presented in MHC-I molecules of tumor cells. These MHC peptide were recognised by Tumor-infiltrating T cells, suggesting an endogenous immune response. In addition, specific T cell clones were capable to kill cell lines endogenously expressing the JET.