Journal
CANCER IMMUNOLOGY RESEARCH
Volume 11, Issue 3, Pages 339-350Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-22-0099
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The PHD/HIF pathway is involved in immune and inflammatory processes, including in the hypoxic tumor microenvironment. Deleting PHD2 in T lymphocytes resulted in regression of EG7-OVA tumors, which depended on HIF-1a. The enhanced control of tumor growth was associated with increased polyfunctionality of CD8+ tumor-infiltrating lymphocytes, indicating the importance of glycolysis in sustaining CTL activity.
The prolyl hydroxylase domain/hypoxia-inducible factor (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 antitumor 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 neo-plastic growth correlated with increased polyfunctionality of CD8+ tumor-infiltrating lymphocytes, as indicated by enhanced expres-sion of IFNy, TNFa, and granzyme B. Phenotypic and transcrip-tomic analyses pointed to a key role of glycolysis in sustaining CTL activity in the tumor bed and identified the PHD2/HIF-1 pathway as a potential target for cancer immunotherapy.
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