Researchers led by Ludwig Lausanne’s Pierpaolo Ginefra and Nicola Vannini reported in an April publication in Cancer Research Communications that the urolithin-A (UroA)—which is produced by the metabolism of ellagic acid by certain types of gut bacteria and has been shown by Nicola’s lab and others to promote mitochondrial health—can also, through an entirely different mechanism, improve T cell surveillance of cancer in mice. Its benefits for mitochondrial health derive from the metabolite’s promotion of mitophagy, or the recycling of damaged and aged mitochondria, a process that slows down with aging. Pierpaolo, Nicola and their colleagues found that UroA activates the transcription factor FOXO1 in CD8+ T cells by reducing its phosphorylation and promoting its localization to the nucleus. Sustained FOXO1 activation boosts the expression of the cell adhesion protein L-selectin, which in turn drives the expansion of naïve T cells in the lymph nodes and spleen of mouse models—and this delays cancer onset. T cells grown in the presence of UroA were also better suppressors of melanoma tumors when transferred into mice. The findings suggest UroA may be a useful nutritional booster of cancer immunosurveillance, though further studies would be required to confirm the relevance of these findings to humans.
Urolithin-A promotes CD8+ T cell-mediated cancer immunosurveillance via FOXO1 activation
Cancer Research Communications, 2024 April 16