A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy.

ABSTRACT: Checkpoint blockade immunotherapies enable the host immune system to recognize and destroy tumour cells. Their clinical activity has been correlated with activated T-cell recognition of neoantigens, which are tumour-specific, mutated peptides presented on the surface of cancer cells. Here we present a fitness model for tumours based on immune interactions of neoantigens that predicts response to immunotherapy. Two main factors determine neoantigen fitness: the likelihood of neoantigen presentation by the major histocompatibility complex (MHC) and subsequent recognition by T cells. We estimate these components using the relative MHC binding affinity of each neoantigen to its wild type and a nonlinear dependence on sequence similarity of neoantigens to known antigens. To describe the evoluti

SUBMITTER: Luksza M 

PROVIDER: S-EPMC6137806 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature