Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development.

ABSTRACT: Metabolic reprogramming is a hallmark of T-cell activation, and metabolic fitness is fundamental for T-cell-mediated antitumor immunity. Insights into the metabolic plasticity of chimeric antigen receptor (CAR) T cells in patients could help identify approaches to improve their efficacy in treating cancer. Here, we investigated the spatiotemporal immunometabolic adaptation of CD19-targeted CAR T cells using clinical samples from CAR T-cell-treated patients. Context-dependent immunometabolic adaptation of CAR T cells demonstrated the link between their metabolism, activation, differentiation, function, and local microenvironment. Specifically, compared with the peripheral blood, low lipid availability, high IL15, and low TGFβ in the central nervous system microenvironment promoted immunomet

SUBMITTER: Goldberg L 

PROVIDER: S-EPMC10984768 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature