Urolithin-A Promotes CD8+ T Cell-mediated Cancer Immunosurveillance via FOXO1 Activation.
Cancer Res Commun
; 4(5): 1189-1198, 2024 May 03.
Article
en En
| MEDLINE
| ID: mdl-38626334
ABSTRACT
Naïve T cells are key players in cancer immunosurveillance, even though their function declines during tumor progression. Thus, interventions capable of sustaining the quality and function of naïve T cells are needed to improve cancer immunoprevention.In this context, we studied the capacity of Urolithin-A (UroA), a potent mitophagy inducer, to enhance T cell-mediated cancer immunosurveillance.We discovered that UroA improved the cancer immune response by activating the transcription factor FOXO1 in CD8+ T cell. Sustained FOXO1 activation promoted the expression of the adhesion molecule L-selectin (CD62L) resulting in the expansion of the naïve T cells population. We found that UroA reduces FOXO1 phosphorylation favoring its nuclear localization and transcriptional activity. Overall, our findings determine FOXO1 as a novel molecular target of UroA in CD8+ T cells and indicate UroA as promising immunomodulator to improve cancer immunosurveillance. SIGNIFICANCE:
Urolithin-A, a potent mitophagy inducer, emerges as a promising tool to enhance cancer immunosurveillance by activating the FOXO1 transcription factor in CD8+ T cells. This activation promotes the expansion of naïve T cells, offering a novel avenue for improving cancer immune response and highlighting UroA as a potential immunomodulator for bolstering our body's defenses against cancer.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD8-positivos
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Cumarinas
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Proteína Forkhead Box O1
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Res Commun
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza