bioRxiv Cancer Biology· Benejova, K., Travis, K., Mathur, D., Song, N. j., Li, Z., Phelps, M. A., Mardis, E., Makowski, L., Carbone, D. P., Owen, D. H., Benej, M. ·· 21 hours agoPickScore67
Targeting alpha-ketoglutarate starvation within the tumor-immune microenvironment rescues T cell effector function in cancer immunotherapy
In brief
A study shows that targeting alpha-ketoglutarate depletion in the tumor immune microenvironment restores T cell effector function and enhances immunotherapy in NSCLC mouse models. In vitro, chronic antigen stimulation and hypoxia rapidly lowered intracellular alpha-ketoglutarate in T cells; supplementation with cell-permeable alpha-ketoglutarate restored effector cytokine production and cytotoxic capacity, restored UTX and JMJD3 activity, and was accompanied by epigenome-wide decreases in H3K27me3.
Why it matters
Links T cell exhaustion to metabolism and epigenetics and provides an experimental route of Ca-aKG supplementation to enhance immunotherapy in NSCLC mice.
Source: bioRxiv Cancer Biology · biorxiv.org