PHD2/3 deletion in CD8 T cells enhances their effector functions and improves tumor response to adoptive cell therapy
(2024)
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- Authors
- Supervisors
- Van den Eynde, Benoît
- Abstract
- Adoptive cell therapy, a promising treatment for hematological malignancies, faces limitations in solid tumors due to the hypoxic and immunosuppressive tumor microenvironment. The transcription factor Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in adaptative response to hypoxia. Here, we aimed to understand the impact of hypoxia and HIF-1α on CD8 T cells with the aim to find new immunotherapy strategies. Using genetic modulations, we deleted or stabilized HIF-1α in CD8 T cells. We observed that HIF-1α stabilization in CD8 T cells led to increased glycolysis, expression of activation markers, and enhanced cytolytic capacity. Furthermore, adoptive transfer of CD8 T cells expressing high levels of HIF-1α resulted in improved tumor control in multiple preclinical models. Finally, stabilization of HIF-1α with the pharmacological inhibitor IOX4 demonstrated potential to enhance the function of human CD8 T cell, offering a promising avenue for improving cancer immunotherapies.
- Affiliations
Citations
Dvorakova, T. (2024). PHD2/3 deletion in CD8 T cells enhances their effector functions and improves tumor response to adoptive cell therapy. https://hdl.handle.net/2078.5/233823