Figure 1.

Adoptive transfer of IL-12/15/18–preactivated NK cells in combination with RT delays RMA-S tumor growth. (a) C57BL/6 mice were s.c. inoculated with 10⁶ RMA-S tumor cells. After 7 d, tumor-bearing mice received 10⁶ NK cells i.v. that were preactivated in vitro with IL-15 or IL-12/15/18 for 16 h. Tumor growth and survival were monitored. The graph of tumor growth displays mean + SEM (n = 5). Survival data are outlined from two experiments (n = 9, 5, and 10 for None, IL-15 NK, and IL-12/15/18 NK groups, respectively) and presented as a Kaplan–Meier survival curve. (b) RMA-S tumor–bearing mice were irradiated with 5 Gy of total body RT on day 7 after tumor cell inoculation. 10⁶ IL-15– or IL-12/15/18–preactivated NK cells were transferred i.v. 3 h after irradiation. The graph of tumor growth displays mean + SEM (n = 5–8). Survival data are outlined from five experiments (n = 24, 38, 11, and 23 for None, RT, RT+IL-15 NK, and RT+IL-12/15/18 NK groups, respectively) and presented as a Kaplan–Meier survival curve. *, P < 0.05; and **, P < 0.01 compared with the group with RT treatment. (c) C57BL/6 mice (n = 10–12) were i.v. injected with 10⁶ B16–RAE-1ε tumor cells and received RT and NK cell infusion (10⁶) at day 7. Lungs were dissected at day 14 after tumor inoculation, and metastases were enumerated by counting the nodules. Numbers of lung metastases from individual mice are indicated, and their geometric mean values are shown. Nodules >500 are depicted as 500. Data are pooled from two independent experiments.