Modified Hypoxia-Inducible Factor Expression in CD8⁺ T Cells Increases Antitumor Efficacy.

ABSTRACT: Adoptive transfer of antitumor cytotoxic T cells is an emerging form of cancer immunotherapy. A key challenge to expanding the utility of adoptive cell therapies is how to enhance the survival and function of the transferred T cells. Immune-cell survival requires adaptation to different microenvironments and particularly to the hypoxic milieu of solid tumors. The hypoxia-inducible factor (HIF) transcription factors are an essential aspect of this adaptation. In this study, we undertook experiments to define structural determinants of HIF that potentiate antitumor efficacy in cytotoxic T cells. We first created retroviral vectors to deliver ectopic expression of HIF1α and HIF2α in mouse CD8⁺ T cells, together or individually and with or without sensitivity to the oxygen-dependent

SUBMITTER: Velica P 

PROVIDER: S-EPMC7611205 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature