TIM-3, TIGIT, and CTLA-4 upregulation in CD8+ T cells with exhaustion features has been reported in chronic lymphocytic leukemia (CLL), AML, and post-allogenic HSCT B-ALL relapse [51,57,58], and targeting these exhaustion markers improved the outcome of hematological malignancies [59]. This evidence concerns the gene CTLA4 and acute lymphoblastic leukemia.