Παρασκευή 21 Σεπτεμβρίου 2018

Evolutionary Pressure against MHC Class II Binding Cancer Mutations

Publication date: Available online 20 September 2018Source: CellAuthor(s): Rachel Marty, Wesley Kurt Thompson, Rany M. Salem, Maurizio Zanetti, Hannah CarterSummaryThe anti-cancer immune response against mutated peptides of potential immunological relevance (neoantigens) is primarily attributed to MHC-I-restricted cytotoxic CD8+ T cell responses. MHC-II-restricted CD4+ T cells also drive anti-tumor responses, but their relation to neoantigen selection and tumor evolution has not been systematically studied. Modeling the potential of an individual's MHC-II genotype to present 1,018 driver mutations in 5,942 tumors, we demonstrate that the MHC-II genotype constrains the mutational landscape during tumorigenesis in a manner complementary to MHC-I. Mutations poorly bound to MHC-II are posi...

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