PHD2 Constrains Antitumor CD8+ T-cell Activity
| Autor: | Charlotte Bisilliat Donnet, Valérie Acolty, Abdulkader Azouz, Anaëlle Taquin, Coralie Henin, Sarah Trusso Cafarello, Sébastien Denanglaire, Massimiliano Mazzone, Guillaume Oldenhove, Oberdan Leo, Stanislas Goriely, Muriel Moser |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Cancer Immunology Research. 11:339-350 |
| ISSN: | 2326-6074 2326-6066 |
| Popis: | 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-1α–dependent manner. The enhanced control of neoplastic growth correlated with increased polyfunctionality of CD8+ tumor-infiltrating lymphocytes, as indicated by enhanced expression of IFNγ, TNFα, and granzyme B. Phenotypic and transcriptomic 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. |
| Databáze: | OpenAIRE |
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