We explored the function of lactate as an epigenetic regulation factor on ectonucleotidases CD39 and CD73, switching ATP to adenosine, and chemokine (C-C motif) receptor 8 (CCR8), a marker of tumor-infiltrating Treg cells, demonstrating the potential of inhibiting lactate production as a strategy for improving CAR-T cells function in GBM treatment. Here, NT5E is linked to glioblastoma.