Beyond Energy Fuel: Ketone Bodies as Multifaceted Modulators of T Cell and Anti-Tumour Immunity.

Abstract

The metabolic programme of T cells is pivotal in determining their differentiation, development and immune function. T cells undergo distinct metabolic reprogramming at various stages. Effector T cells primarily utilise glycolysis to generate energy quickly, whereas memory T cells depend on fatty acid oxidation (FAO) to sustain long-term survival and enable rapid reactivation. This metabolic differentiation is regulated through metabolic reprogramming by adjusting nutrient utilisation to meet specific demands. Ketone bodies, FAO-derived metabolites, interact with glucose and amino acid metabolism to influence the function and differentiation of T cells and other immune cell subsets. The body's metabolic equilibrium is significantly influenced by dietary patterns. A medically designed dietary intervention that elevates ketone body levels can reshape T-cell metabolism, influencing their differentiation, development and immune functions. This metabolic modulation suggests a potential interplay between nutritional strategies and T-cell immunotherapy applications, especially in the context of tumour immunology. This review explores ketone body metabolism and its impact on T-cell function, offering insights into the clinical use of diet-induced ketosis for T-cell immunotherapy. It also emphasises the potential of metabolic reprogramming to boost T cell performance and improve the efficacy of immunotherapy.