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Urolithin-A Promotes CD8+ T Cell-mediated Cancer Immunosurveillance via FOXO1 Activation
Pierpaolo Ginefra1, Helen Carrasco Hope1, Yi-Hsuan Chiang1
1Department of Oncology, Ludwig Institute for Cancer Research Lausanne, University of Lausanne, Lausanne, Switzerland.
Cancer Research Communications
|April 16, 2024
Summary
Urolithin-A enhances cancer immunosurveillance by activating the FOXO1 transcription factor in CD8+ T cells. This promotes the expansion of naïve T cells, improving the immune response against cancer.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Naïve T cells are crucial for cancer immunosurveillance but decline during tumor progression.
- Interventions are needed to maintain naïve T cell function for improved cancer immunoprevention.
Purpose of the Study:
- To investigate Urolithin-A's capacity to enhance T cell-mediated cancer immunosurveillance.
- To explore Urolithin-A's mechanism of action in T cells.
Main Methods:
- Studied the effect of Urolithin-A (UroA) on T cells.
- Analyzed the activation of transcription factor FOXO1 in CD8+ T cells.
- Assessed the expression of L-selectin (CD62L) and T cell populations.
Main Results:
- Urolithin-A activated FOXO1 in CD8+ T cells.
- FOXO1 activation led to increased L-selectin expression and naïve T cell expansion.
- Urolithin-A reduced FOXO1 phosphorylation, promoting its nuclear localization and activity.
Conclusions:
- FOXO1 is a novel molecular target of Urolithin-A in CD8+ T cells.
- Urolithin-A shows promise as an immunomodulator to enhance cancer immunosurveillance.
- Sustaining naïve T cell populations may improve cancer immunoprevention strategies.
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