To test our hypothesis, we generated Treg cell–specific AMPKα1- and AMPKα2-deficient mice (Prkaa1fl/flPrkaa2fl/flFoxp3YFP–Cre, referred to here as Prkaa1/2fl/flFoxp3YFP–Cre mice) and challenged them with either subcutaneous B16 melanoma tumors or intratracheal inoculations of influenza A/WSN/33 H1N1 virus, disease models whose outcomes are dependent on Treg cell function and whose microenvironments are burdened with metabolic derangements that challenge cellular metabolism (4, 23). This evidence concerns the gene PRKAA1 and melanoma.