Flt3L administration augments an anti-AML immune resistance via the generation of NK effector cells while DC vaccinations generate both NK and T-cell effector cells.
(A) Flt3L (30 μg per dose) was administered from days −10 to +11. A separate cohort of mice was untreated. On day 0, mice were challenged with C1498 cells (2 × 105 cells per mouse). Flt3L-treated mice were injected with no mAb (n = 20) or either irrelevant rat IgG mAb, anti-NK1.1 mAb, or anti-Thy1.2 mAb (n = 10 per group) beginning on day −2 and continuing weekly until day 54 as described in “Materials and methods.” The actuarial survival rate of Flt3L-treated recipients was significantly higher than non-treated controls (P = .00069). The actuarial survival rate of Flt3L-treated recipients given irrelevant rat IgG mAb was significantly higher than those given anti-Thy1.2 (P = .005) or anti-NK1.1 (P = .0077). NK depletion eliminated all of the protective effect of Flt3L treatment (P = .065 vs non–Flt3L-treated controls). (B) (C) In a separate experiment, recipients were vaccinated with DC cells (0.5 × 106cells per mouse) on days −21, −14, and −7 or were left untreated. Mice then were randomized to receive irrelevant (panels B, C), anti-NK1.1 (panel B), or anti-CD4 plus anti-CD8 (panel C) mAb from days −1 to +27 post-BMT. NK depletion resulted in a lower survival rates in non-treated control recipients (P = .0005) and in DC-vaccinated recipients (P = .016). DC-vaccinated mice depleted of NK cells had a higher survival rate than NK-depleted controls (P = .0095) and nonvaccinated, nondepleted controls (P = .036), indicating that NK cells were not the only cell population responsible for C1498 resistance. Depletion of T cells reduced survival rates in DC-vaccinated mice from 30% to 10% although these differences did not reach statistical significance (P = .15).
