Data from Urolithin-A Promotes CD8<sup>+</sup> T Cell–mediated Cancer Immunosurveillance via FOXO1 Activation

Abstract

<div>Abstract<p>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.</p><p>In this context, we studied the capacity of Urolithin-A (UroA), a potent mitophagy inducer, to enhance T cell–mediated cancer immunosurveillance.</p><p>We discovered that UroA improved the cancer immune response by activating the transcription factor FOXO1 in CD8<sup>+</sup> 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<sup>+</sup> T cells and indicate UroA as promising immunomodulator to improve cancer immunosurveillance.</p>Significance:<p>Urolithin-A, a potent mitophagy inducer, emerges as a promising tool to enhance cancer immunosurveillance by activating the FOXO1 transcription factor in CD8<sup>+</sup> 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.</p></div>