Aging-Driven Immunosuppression: The Role of Tregs in the Ovarian Tumor Microenvironment
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Epithelial ovarian cancer (EOC) incidence and mortality increase with age, driven in part by chronic inflammation, diminished T cell output, and heightened regulatory T cell (Treg)-mediated immunosuppression. In aged EOC-bearing mice, we observed reduced survival, accompanied by impaired CD4⁺ and CD8⁺T cell responses and a marked expansion of FOXP3⁺ Tregs exhibiting elevated IL-10 and TGFβ expression. Metabolic profiling revealed enhanced oxidative phosphorylation in Tregs from aged mice, along with a fivefold increase in intracellular succinate levels. This accumulation of succinate within the aged tumor microenvironment was found to potentiate Treg suppressive function. Notably, pharmacologic inhibition of α-ketoglutarate dehydrogenase reversed this effect, restoring effector T cell activity. These findings highlight succinate driven metabolic reprogramming as a central mechanism of age related Treg dysfunction in EOC and suggest that targeting succinate metabolism may offer a promising strategy to rejuvenate antitumor immunity in elderly patients.
