Low immunogenicity of common cancer hot spot mutations resulting in false immunogenic selection signals.

ABSTRACT: Cancer is driven by somatic mutations that result in a cellular fitness advantage. This selective advantage is expected to be counterbalanced by the immune system when these driver mutations simultaneously lead to the generation of neoantigens, novel peptides that are presented at the cancer cell membrane via HLA molecules from the MHC complex. The presentability of these peptides is determined by a patient's MHC genotype and it has been suggested that this results in MHC genotype-specific restrictions of the oncogenic mutational landscape. Here, we generated a set of virtual patients, each with an identical and prototypical MHC genotype, and show that the earlier reported HLA affinity differences between observed and unobserved mutations are unrelated to MHC genotype variation. We demonst

SUBMITTER: Claeys A 

PROVIDER: S-EPMC7895404 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature