CTLA-4 is a competitive receptor for the B7-1 and -2 ligands which normally bind to CD28, leading to activation and proliferation of T cells.53,54 In addition, regulatory T-cells (Tregs) constitutively express CTLA-4 where, in contrast to other T-cells, it is a critical negative regulator of T-cell responses.55 Hence, CTLA-4 blockade maintains effector T-cell activation and proliferation and sustains an anti-tumor response (Figure 2).55 Unfortunately, the modest response to PD-1/PD-L1 inhibitors in patients with DMG is mirrored by CTLA-4 antibodies. This evidence concerns the gene CTLA4 and neoplasm.