Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma
There are no effective approaches to overcome the immunosuppressive activity of tumor-associated macrophages (TAMs). De Leo et al. report that monocyte-derived macrophages (MDMs), but not microglia (MGs), are major contributors to the immunosuppression associated with TAMs in glioblastoma and demonstrate that PERK-perturbed glucose metabolism drives MDM immunosuppressive programs via histone lactylation. Targeting of PERK-driven histone lactylation boosts the effect of immunotherapy.