Here, we used well-defined human CD33+ AML cell lines and genetically engineered sublines to test the impact of inhibitory (PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273)) and activating (CD80 (B7-1) and CD86 (B7-2)) T-cell ligands on the cytolytic activity of AMG 330 in vitro, and then conducted proof-of-principle studies in specimens obtained from patients with AML. Here, PDCD1LG2 is linked to acute myeloid leukemia.