A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8⁺ T cell fitness in solid tumours.

ABSTRACT: Reprogramming T cell metabolism can improve intratumoural fitness. By performing a CRISPR/Cas9 metabolic survey in CD8⁺ T cells, we identified 83 targets and we applied single-cell RNA sequencing to disclose transcriptome changes associated with each metabolic perturbation in the context of pancreatic cancer. This revealed elongation of very long-chain fatty acids protein 1 (Elovl1) as a metabolic target to sustain effector functions and memory phenotypes in CD8⁺ T cells. Accordingly, Elovl1 inactivation in adoptively transferred T cells combined with anti-PD-1 showed therapeutic efficacy in resistant pancreatic and melanoma tumours. The accumulation of saturated long-chain fatty acids in Elovl1-deficient T cells destabilized INSIG1, leading to SREBP2 activation, incr

SUBMITTER: Pretto S 

PROVIDER: S-EPMC11946891 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature