Frequency-dependent selection of neoantigens fosters tumor immune escape and predicts immunotherapy response.

ABSTRACT: Cancer is an evolutionary process shaped by selective pressure from the microenvironments. However, recent studies reveal that certain tumors undergo neutral evolution where there is no detectable fitness difference amongst the cells following malignant transformation. Here, through computational modeling, we demonstrate that negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is highly similar to neutral evolution. Crucially, NFDS promotes high antigenic heterogeneity and early immune evasion in hypermutable tumors, leading to poor responses to immune checkpoint blockade (ICB) therapy. Our model also reveals that NFDS is characterized by a negative association be

SUBMITTER: Chen S 

PROVIDER: S-EPMC11199503 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature