Myeloid-specific KDM6B inhibition sensitizes Glioblastoma to PD1 blockade

Targeting epigenetic pathways to reprogram the functional phenotype of immune-suppressive myeloid cells to overcome resistance to ICT remains unexplored. Single-cell and spatial transcriptomic analysis of human GBM tumors demonstrated high expression of an epigenetic enzyme- histone 3 lysine 27 demethylase (KDM6B) in the intra-tumoral immune-suppressive myeloid cell subsets. Using preclinical models of GBM with genetic deletion of KDM6B and pharmacological inhibition of KDM6B along with ICT, we assessed the reprogramming of the myeloid cells in the GBM tumor microenvironment.