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. PHD2-deltaT vs. WT