PHD2 constrains the anti-tumor CD8+ T cell activity

The PHD/HIF pathway has been implicated in a wide range of immune and inflammatory processes, including in the oxygen-deprived tumor microenvironment. To examine the effect of HIF stabilization in anti-tumor immunity, we deleted Phd2 selectively in T lymphocytes using the cre/lox system. We show that the deletion of PHD2 in lymphocytes resulted in enhanced regression of EG7-OVA tumors, in a HIF-1a?dependent manner. The enhanced control of neoplastic growth correlated with increased poly-functionality of CD8+ tumor-infiltrating lymphocytes, i.e. enhanced expression of IFN-g, TNF-a and granzyme B. Phenotypic and transcriptomic analyses point to a key role of glycolysis in sustaining CTL activity in the tumor bed and identifies the PHD2/HIF-1 pathway as potential target for intervention. Overall design: PHD2-deltaT vs. WT