Palmitate-induced mitochondrial damage restricts histone acetylation in CD8 T cells to impair antitumor immunity - PubMed
6 hours ago
- #SPHK2 inhibition
- #mitochondrial dysfunction
- #CD8 T cells
- Palmitate (PA) accumulation in solid tumors impairs CD8 T cell (CTL) mitochondrial metabolism, leading to reduced effector functions and compromised antitumor immunity.
- PA-induced mitochondrial dysfunction decreases histone acetylation and chromatin accessibility, suppressing gene expression for T cell replication and effector programs.
- Sphingosine kinase 2 (SPHK2) is a key mediator in this process; inhibiting SPHK2 restores mitochondrial fitness, rescues CTL function, and enhances antitumor activity.
- The study highlights a mechanism for PA-driven immune evasion and identifies SPHK2 as a potential therapeutic target in T cell-based immunotherapies.