Figure 1.

The scheme of immune checkpoint molecules associated with anti-leukemic immunity. Direct cytotoxicity in leukemic cells is attenuated by the binding of programmed cell death-1 (PD-1) on T cells and programmed cell death-ligand 1 (PD-L1) on cancer cells. T-cell activation via B7 family molecules on dendritic cells is canceled by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Phagocytic activity of macrophages is dampened by the “don’t eat me” signals of CD47 on leukemic cells. Lymphocyte activation gene-3 protein (LAG-3) expressed on T cells or natural killer cells inhibit the activity of CD4-positive T cells. T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) has multiple inhibitory mechanisms such as attenuation of natural killer (NK) cell activity/stabilization of regulatory T cells by binding to galectin-9 and neutralizing the pro-inflammatory effect of HMGB1 and phosphatidylserine (PtdSer).