Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8⁺ T cells and impede CAR T-cell efficacy.

ABSTRACT: In chronic lymphocytic leukemia (CLL), acquired T-cell dysfunction impedes development of effective immunotherapeutic strategies, through as-yet unresolved mechanisms. We have previously shown that CD8⁺ T cells in CLL exhibit impaired activation and reduced glucose uptake after stimulation. CD8⁺ T cells in CLL patients are chronically exposed to leukemic B cells, which potentially impacts metabolic homeostasis resulting in aberrant metabolic reprogramming upon stimulation. Here, we report that resting CD8⁺ T cells in CLL have reduced intracellular glucose transporter 1 (GLUT1) reserves, and have an altered mitochondrial metabolic profile as displayed by increased mitochondrial respiration, membrane potential, and levels of reactive oxygen species. This coin

SUBMITTER: van Bruggen JAC 

PROVIDER: S-EPMC7022375 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature