Article Figures & Data
Figures
- FIGURE 1.
The dose and timing of IL-12 treatment dictate the relative roles of NK cells and NKT cells in its anti-metastatic effect against B16F10 melanoma. a, Groups of five B6, B6.pfp−/−, B6.IFN-γ−/−, or B6.Jα281−/− mice or B6 mice treated with anti-NK1.1 mAb on days −2, 0 (the day of B16F10 tumor inoculation), and 7 were inoculated i.v. with decreasing numbers (5 × 105, 1 × 105, 5 × 104) of B16F10 tumor cells as indicated. b, Groups of 5–10 mice, as described above, including B6.RAG-1−/− mice, were inoculated i.v. with 5 × 105 B16F10 tumor cells (untreated). Similar groups of mice were treated i.p. with 250 U of IL-12 on days −5, −4, −3, −2, −1 before and days 1–5 after B16F10 tumor inoculation (high). c, Groups of five B6, B6.Jα281−/−, B6.pfp−/−, and B6.IFN-γ−/− mice or B6 mice treated with anti-NK1.1 mAb were inoculated i.v. with 5 × 105 B16F10 tumor cells (untreated). Similar groups of mice were treated i.p. with 250 U of IL-12 on days 3–12 after B16F10 tumor inoculation (delayed) or with 50 U of IL-12 on days −5, −4, −3, −2, and −1 before and days 1–5 after tumor inoculation (low). In all experiments, 14 days after tumor inoculation the lungs of these mice were harvested, and colonies were counted and recorded as the mean number of colonies ± SE. Asterisks indicate the groups in which IL-12 treatment significantly enhanced that group’s number of lung metastases above that in the same treated control wild-type B6 mice (by Mann-Whitney test: ∗, p < 0.05; ∗∗, p < 0.01).
- FIGURE 2.
NK cells and pfp are sufficient for the anti-metastatic effect of IL-12 against EL4-S3 lymphoma. a, Groups of 10 B6, B6.Pfp−/−, B6.IFN-γ−/−, B6.RAG-1−/−, or B6.Jα281−/− mice or B6 mice treated with anti-NK1.1 mAb on days −2, 0 (the day of B16F10 tumor inoculation), and 7 were inoculated i.v. with 5 × 103 EL4-S3 tumor cells as indicated. b, Groups of mice as described above were inoculated i.v. with 5 × 104 EL4-S3 tumor cells (untreated). Similar groups of mice were treated i.p. with 250 U of IL-12 on days −5, −4, −3, −2, and −1 before and days 1–5 after EL4-S3 tumor inoculation (high). c, Groups of 5–10 B6 and B6.Jα281−/− mice or B6 mice treated with anti-NK1.1 mAb were inoculated i.v. with 5 × 104 EL4-S3 tumor cells (untreated). Similar groups of mice were treated i.p. with 250 U of IL-12 on days 3–12 after EL4-S3 tumor inoculation (delayed) or with 50 U of IL-12 on days −5, −4, −3, −2, and −1 before and days 1–5 after tumor inoculation (low). In all experiments, 14 days after tumor inoculation the lungs of these mice were harvested and fixed, and colonies counted and recorded as the mean number of colonies ± SE. Asterisks indicate the groups in which IL-12 treatment significantly enhanced that group’s number of lung metastases above that in control wild-type treated B6 mice (by Mann-Whitney test: ∗, p < 0.05; ∗∗, p < 0.01).
- FIGURE 3.
RM-1: NK cells, NKT cells, pfp, and IFN-γ contribute to the anti-metastatic effect of IL-12. a, Groups of 5–10 B6, B6.pfp−/−, B6.IFN-γ−/−, B6.RAG-1−/−, and B6.Jα281−/− mice or B6 mice treated with anti-NK1.1 mAb (on days −2, 0 (the day of i.v. RM-1 tumor inoculation), and 7) were inoculated s.c. 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 1 × 104 RM-1 cells were injected i.v. via the tail vein. b, Groups of mice as described above were inoculated i.v. with 1 × 105 RM-1 tumor cells (untreated). Similar groups of mice were treated i.p. with 250 U of IL-12 on days −5, −4, −3, −2, and −1 before and days 1–5 after RM-1 tumor inoculation (high). c, Groups of 5–10 B6 and B6.Jα281−/− mice or B6 mice treated with anti-NK1.1 mAb were inoculated i.v. with 1 × 105 RM-1 tumor cells (untreated). Similar groups of mice were treated i.p. with 250 U of IL-12 on days 3–12 after RM-1 tumor inoculation (delayed) or with 50 U of IL-12 on days −5, −4, −3, −2, and −1 before and days 1–5 after tumor inoculation (low). In all experiments, 14 days after tumor inoculation the lungs of these mice were harvested and fixed, and colonies were counted and recorded as the mean number of colonies ± SE. Asterisks indicate the groups in which IL-12 treatment significantly enhanced that group’s number of lung metastases above that in control wild-type treated B6 mice (by Mann-Whitney test: ∗, p < 0.05; ∗∗, p < 0.01).
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