The metabolic reprogramming that drives immunity engages the mevalonate pathway for cholesterol biosynthesis and protein prenylation. The importance of tight regulation of this metabolic route is reflected by the fact that too low activity impairs cellular function and survival, whereas hyperactivity can lead to malignant transformation. Here, we first address how mevalonate metabolism drives immunity and then highlight ways of the immune system to respond to both, limited and uncontrolled flux through the mevalonate pathway. Immune responses elicited by mevalonate pathway dysregulation may be harnessed to increase the clinical efficacy of current cancer therapy regimens.
Keywords: ATP citrate lyase; HMG-CoA reductase; T lymphocytes; cancer; cholesterol; dendritic cells; flux; immunometabolism; macrophages; mevalonate; protein prenylation.