Blockade of 6-phosphogluconate dehydrogenase generates CD8+ effector T cells with enhanced anti-tumor function
Saeed Daneshmandi, Teresa Cassel, Penghui Lin, Richard M. Higashi, Gerburg M. Wulf, Vassiliki A. Boussiotis, Teresa W.‐M. Fan, Pankaj Seth
Abstract
T effector cells. These cells have gene signatures and immunogenic markers of effector phenotype and show potent anti-tumor functions both in vitro and in vivo. In these cells, metabolic reprogramming occurs along with increased mitochondrial ROS and activated antioxidation machinery to balance ROS production against oxidative damage. Our findings reveal a role of 6PGD as a checkpoint for T cell effector differentiation/survival and evidence for 6PGD as an attractive metabolic target to improve tumor immunotherapy.
Topics & Concepts
EffectorBlockadeFunction (biology)CD8Cell biologyChemistryCytotoxic T cellCancer researchDehydrogenaseBiologyEnzymeBiochemistryImmunologyReceptorAntigenIn vitroCancer, Hypoxia, and MetabolismCytomegalovirus and herpesvirus researchImmune Cell Function and Interaction