AUTHOR=Bargiela David , Cunha Pedro P. , Veliça Pedro , Krause Lena C. M. , Brice Madara , Barbieri Laura , Gojkovic Milos , Foskolou Iosifina P. , Rundqvist Helene , Johnson Randall S. 

TITLE=The factor inhibiting HIF regulates T cell differentiation and anti-tumour efficacy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1293723

DOI=10.3389/fimmu.2024.1293723

ISSN=1664-3224

ABSTRACT=The hypoxia-inducible factor (HIF) transcription factors play a key role in T cell activation and their adaptation to physiological changes in oxygen tensions. HIF transcriptional activity is regulated by the asparaginyl hydroxylase, factor inhibiting HIF (FIH). The role of FIH in determining T cell fate and function remains unknown.We generated T cell-specific knockout mice to profile the effects of FIH across a range of HIF and oxygen levels. Our results show that FIH regulates T cell function in a HIF-dependent manner, and is most active at intermediate, physiological oxygen tensions. Loss of FIH in T cells augments in vivo T cell expansion and improves T cell anti-tumour activity in mice. These results support FIH inhibition within T cells as a potential immunotherapy strategy.