Lack of detectable neoantigen depletion signals in the untreated cancer genome
Menée à l'aide de données génomiques du projet "The Cancer Genome Atlas" portant sur 33 types de cancers et menée à l'aide d'une simulation de mutations au niveau des gènes du système HLA codant pour le peptide de liaison du complexe majeur d'histocompatibilité CMH I, cette étude met en évidence, dans la plupart des tumeurs non traitées, l'absence de signaux détectables révélant un appauvrissement des néoantigènes
Somatic mutations can result in the formation of neoantigens, immunogenic peptides that are presented on the tumor cell surface by HLA molecules. These mutations are expected to be under negative selection pressure, but the extent of the resulting neoantigen depletion remains unclear. On the basis of HLA affinity predictions, we annotated the human genome for its translatability to HLA binding peptides and screened for reduced single nucleotide substitution rates in large genomic data sets from untreated cancers. Apparent neoantigen depletion signals become negligible when taking into consideration trinucleotide-based mutational signatures, owing to lack of power or to efficient immune evasion mechanisms that are active early during tumor evolution.
Nature Genetics 2019