Dietary restriction reprograms CD8⁺ T cell fate to enhance anti-tumour immunity and immunotherapy responses.

ABSTRACT: Reducing calorie intake through dietary restriction (DR) slows tumour growth in mammals, yet the underlying mechanisms are poorly defined. Here, we show that DR enhances anti-tumour immunity by optimizing CD8⁺ T cell function within the tumour microenvironment (TME). Using syngeneic xenograft tumour models, we found that DR induces a profound reprogramming of CD8⁺ T cell fate in the TME, favouring the expansion of effector T cell subsets with enhanced metabolic capacity and cytotoxic potential, while limiting the accumulation of terminally exhausted T cells. This metabolic reprogramming is driven by enhanced ketone body oxidation, particularly β-hydroxybutyrate (βOHB), which is elevated in both the circulation and tumour tissues of DR-fed mice. βOHB fuels T cell oxida

SUBMITTER: Oswald BM 

PROVIDER: S-EPMC12727518 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature