NK- and NKT-cell–mediated control of experimental tumor metastasis by independent pfp and IFN-γ activities.

(A) B6, B6.pfp⁰, B6.RAG-1⁰, B6.TNF⁰, B6.IFN-γ⁰, and B6.gldmice or B6 mice treated with anti-NK1.1 were inoculated subcutaneously between the shoulder blades with RM-1 tumor cells (2 × 10⁶), and tumors were allowed to establish for 9 days. Subcutaneous tumors were then resected and a dose range of RM-1 cells (as indicated) injected through the tail vein. Mice were killed 14 days later, the lungs were removed and fixed, and colonies were counted and recorded as the mean number of colonies ± SE. A group of B6 mice was depleted of NK1.1⁺ cells in vivo by mAb treatment (100 μg/injection) on days −2, 0 (day of intravenous tumor inoculation), 2, and 9. (B) B6, B6.pfp⁰, B6.IFN-γ⁰, and B6.pfp⁰.IFN-γ⁰mice or B6 and B6.pfp⁰ mice treated with anti–mIFN-γ mAb (500 μg/injection) or control mAb (500 μg/injection) were treated as above. Mice received anti–IFN-γ mAb on days −2, 0 (day of intravenous tumor inoculation), 2, 7, and 10, with some groups receiving anti–mIFN-γ mAb early (days −2, 0) or late (days 7, 10). (A) Significant differences from the B6 group were determined by a Mann-Whitney U test (*P < .0001). Additionally, mice treated with anti-NK1.1 had significantly more metastases than any other group, including B6.pfp⁰ and B6.IFN-γ⁰ mice (P < .0001). (B) Significant differences from the B6.pfp⁰ group were determined by a Mann-Whitney U test and denoted (*P < .0001). The number of mice per group is shown in parentheses.