For example, TIM-3+PD-1+CD8+ T cells in mice with advanced AML exhibited severe exhausted phenotype as defined by failure to produce IL-2, tumor necrosis factor and interferon-γ, and combined targeting of TIM-3 and PD-1 pathways was more effective in controlling the leukemia burden (10). This evidence concerns the gene HAVCR2 and acute myeloid leukemia.