CD4 and central nervous system cancer: While killing activity of H3K27M-specific CD8+ T cells against HLA-A*02+ tumor cells with endogenous H3.3K27M expression remains controversial17–19 we have recently demonstrated that CD4+ T cell interaction with peptide MHC class II in glioma-infiltrating myeloid cells is critical for the fitness of glioma-infiltrating CD8+ T cells22.