Low-avidity T cells drive endogenous tumor immunity in mice and humans.

ABSTRACT: T cells recognize neoepitope peptide-major histocompatibility complex class I on cancer cells. The strength (or avidity) of the T cell receptor-peptide-major histocompatibility complex class I interaction is a critical variable in immune control of cancers. Here, we analyze neoepitope-specific CD8 cells of distinct avidities and show that low-avidity T cells are the sole mediators of cancer control in mice and are solely responsive to checkpoint blockade in mice and humans. High-avidity T cells are ineffective and immune-suppressive. The mechanistic basis of these differences lies in the higher exhaustion status of high-avidity cells. High-avidity T cells have a distinct transcriptomic profile that is used here to calculate an 'avidity score', which we then use for in silico identification

SUBMITTER: Singhaviranon S 

PROVIDER: S-EPMC11785530 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature