CD4 and neoplasm: Recently, serval studies have shown that the tumor immune microenvironment (TIME) has critical roles in DIPG: (i) Tumor-infiltrating cells (TILs) including Treg, CD4 T cells, NK, B cells, monocytes and eosinophils have been identified in H3K27M mutant DIPGs [110]; (ii) Expression of indoleamine 2,3 dioxygenase 1 (IDO1), an immunosuppressive enzyme that metabolizes tryptophan, is low in cultured DIPG cells.