Glycolysis inhibition affects proliferation and cytotoxicity of Vγ9Vδ2 T cells expanded for adoptive cell therapy.
Cytotherapy
; 26(9): 1033-1045, 2024 Sep.
Article
en 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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fosforilación Oxidativa
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Inmunoterapia Adoptiva
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Receptores de Antígenos de Linfocitos T gamma-delta
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Proliferación Celular
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Glucólisis
Límite:
Humans
Idioma:
En
Revista:
Cytotherapy
Asunto de la revista:
TERAPEUTICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Noruega