Simulating CD8 T cell exhaustion: A comprehensive approach.

ABSTRACT: Immunotherapy has transformed cancer treatment but benefits only some patients, and predictive biomarkers are lacking. One correlate of response is the reinvigoration of a subset of CD8 T cells that have an exhausted phenotype and impaired functionality. To develop effective therapies, reproducible models are required to identify candidate target genes that enable reversal of T cell exhaustion. Here, we describe an in vitro model by chronically stimulating T cells with their cognate antigen, followed by temporal phenotypic characterization. This model recapitulates many critical hallmarks of exhaustion, including expression of canonical surface markers, impaired proliferation, reduced cytokine production, decreased cytotoxic granule release, and metabolic alterations. Two in vivo

SUBMITTER: Manrique-Rincon AJ 

PROVIDER: S-EPMC12268933 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature