Fig. 7

The mechanism of reduced intracellular lactate induced by oxamate leading to H3K18 lactylation on CD39, CD73 and CCR8 gene promotors. Oxamate inhibits lactate production and release into TME. Reduced lactate in GSCs and T cells suppresses histone H3K18 lactylation, leading to the decrease of CD73 gene promotor activity. Low level of H3K18 lactylation restrains the activity of CD39 gene promotor in Treg cells and macrophages. The conversion of ATP to AMP then to adenosine is inhibited by reduced levels of CD39 and CD73, respectively. Reduced CCR8 level due to low H3K18 lactylation blocks the binding to its ligands CCL1 and CCL18 secreted by macrophages. Oxamate changes the immunosuppressive microenvironment of GBM and improves the effect of CAR-T therapy