Harnessing nutrient scarcity for enhanced CAR-T-cell potency and safety in solid tumors.

ABSTRACT: Despite significant advancements, the effectiveness of chimeric antigen receptor (CAR)-T-cell-based therapies in solid tumors remains limited. Key challenges include on-target effects, off-tumor toxicity and reduced CAR-T-cell function within the tumor microenvironment, which is often characterized by metabolic stress triggered by factors such as amino acid scarcity. Activating transcription factor-4 (ATF4) and its upstream regulator GCN2 play crucial roles in the metabolic reprogramming and functionality of CD4⁺ and CD8⁺ T cells. ATF4 can be activated by various cellular stress signals, including amino acid deprivation. While ATF4 activation may be associated with T-cell dysfunction, its role in stress adaptation presents an opportunity for therapeutic intervention-p

SUBMITTER: Manchon E 

PROVIDER: S-EPMC12125372 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature