Glycolysis inhibition affects proliferation and cytotoxicity of Vγ9Vδ2 T cells expanded for adoptive cell therapy.
Cytotherapy
; 26(9): 1033-1045, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38775775
ABSTRACT
BACKGROUND AIMS:
Vγ9Vδ2 T cells are under investigation as alternative effector cells for adoptive cell therapy (ACT) in cancer. Despite promising in vitro results, anti-tumor efficacies in early clinical studies have been lower than expected, which could be ascribed to the complex interplay of tumor and immune cell metabolism competing for the same nutrients in the tumor microenvironment.METHODS:
To contribute to the scarce knowledge regarding gamma delta T-cell metabolism, we investigated the metabolic phenotype of 25-day-expanded Vγ9Vδ2 T cells and how it is intertwined with functionality.RESULTS:
We found that Vγ9Vδ2 T cells displayed a quiescent metabolism, utilizing both glycolysis and oxidative phosphorylation (OXPHOS) for energy production, as measured in Seahorse assays. Upon T-cell receptor activation, both pathways were upregulated, and inhibition with metabolic inhibitors showed that Vγ9Vδ2 T cells were dependent on glycolysis and the pentose phosphate pathway for proliferation. The dependency on glucose for proliferation was confirmed in glucose-free conditions. Cytotoxicity against malignant melanoma was reduced by glycolysis inhibition but not OXPHOS inhibition.CONCLUSIONS:
These findings lay the groundwork for further studies on manipulation of Vγ9Vδ2 T-cell metabolism for improved ACT outcome.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidative Phosphorylation
/
Immunotherapy, Adoptive
/
Receptors, Antigen, T-Cell, gamma-delta
/
Cell Proliferation
/
Glycolysis
Limits:
Humans
Language:
En
Journal:
Cytotherapy
Journal subject:
TERAPEUTICA
Year:
2024
Type:
Article
Affiliation country:
Norway