Mechanistically, lactate-induced histone lactylation upregulates TET2, which, using STAT3 as a bridge, modulates ARG1 promoter methylation to upregulate its expression and ultimately enhance the immunosuppressive function of MDSCs.<h4>Conclusion</h4>This research reveals that the histone lactylation-mediated alteration of TET2 presents a novel therapeutic target for cancer treatment. Here, STAT3 is linked to cancer.