Lack of detectable neoantigen depletion signals in the untreated cancer genome.

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Somatic mutations can result in the formation of neoantigens, immunogenic peptides that are presented on the tumor cell surface via HLA molecules. These mutations are expected to be under negative selection pressure, but the extent of the resulting neoantigen depletion remains unclear. Based on 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 datasets from untreated cancers. Apparent neoantigen depletion signals became negligible when considering trinucleotide-based mutational signatures, either due to lack of power or efficient immune evasion mechanisms active early during tumor evolution.