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- Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in patients with lung cancer
Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in patients with lung cancer
Auteurs
Antonela Merlotti, Benjamin Sadacca, Yago A. Arribas, Mercia Ngoma, Marianne Burbage, Christel Goudot, Alexandre Houy, Ares RocañÃn-Arjó, Ana Lalanne, Agathe Seguin-Givelet, Marine Lefevre, Sandrine Heurtebise-Chrétien, Blandine Baudon, Giacomo Oliveira, Damarys Loew, Montserrat Carrascal, Catherine J. Wu, Olivier Lantz, Marc-Henri Stern, Nicolas Girard, Joshua J. Waterfall, Sebastian Amigorena
Résumé
Although most characterized tumor antigens are encoded by canonical transcripts (such as differentiation or tumor-testis antigens) or mutations (both driver and passenger mutations), recent results have shown that noncanonical transcripts including long noncoding RNAs and transposable elements (TEs) can also encode tumor-specific neo-antigens. Here, we investigate the presentation and immunogenicity of tumor antigens derived from noncanonical mRNA splicing events between coding exons and TEs. Comparing human non–small cell lung cancer (NSCLC) and diverse healthy tissues, we identified a subset of splicing junctions that is both tumor specific and shared across patients. We used HLA-I peptidomics to identify peptides encoded by tumor-specific junctions in primary NSCLC samples and lung tumor cell lines. Recurrent junction-encoded peptides were immunogenic in vitro, and CD8
Membres

MARC-HENRI STERN
Directeur de recherche
SEBASTIAN AMIGORENA
Directeur de recherche CNRS
CHRISTEL GOUDOT
Ingénieur de recherche
OLIVIER LANTZ
Médecin
MARIANNE BURBAGE
Chargé de recherche Inserm