Lirilumab therapy improves survival in a prophylactic HLA⁺tumor model in an NK-cell–dependent manner. (A) Schema of antibody administration. (B) To determine whether HLA⁺ tumors escape NK-cell control in KIR Tg mice, (□) 221 (n = 7) or (○) 221 HLA-Cw3 (n = 7) tumor cells (10⁷ cells) were injected intravenously into Rag1KO-Tg KIR mice, including (▪) one group injected with 221 tumor cells (10⁷ cells) in which NK cells were depleted with 100 µg of anti-NK1.1 mAb (n = 7). (C) Rag1KO-Tg KIR mice were injected intravenously with 221 HLA-Cw3 tumor cells (10⁷ cells) and subsequently received either (○) no treatment (n = 7), (♢) IC mAb at 15 mg/kg, (●) lirilumab at 15 mg/kg (n = 6), or (▪) lirilumab at 15 mg/kg and 100 µg anti-NK1.1 mAb (n = 6) to deplete NK cells. NK-cell depletion was started on the day prior to tumor challenge and was maintained by injecting 100 µg anti-NK1.1 every 10 days. Mice were then monitored for overall survival. *P < .001. (B) and (C) show several groups of the same experiments. One experiment representative of 3 experiments is shown.