Wang et al. identify a metabolic-immune feedback circuit in hepatocellular carcinoma, in which tumor cell-intrinsic AARS1-mediated ATF6 lactylation activates the TDO2-kynurenine axis to promote Treg differentiation and immunosuppression, while Treg-derived eNAMPT enhances tumor glycolysis and lactate production, revealing a therapeutic vulnerability to AARS1 inhibition combined with PD-1/PD-L1 blockade.