Fig. 1.

a Nonmyeloablative conditioning with Cy augments endogenous antitumor immunity without the need for hematopoietic cell transplantation. Cy alone increases tumor-free survival. i Experimental schema. ii BALB/c mice were injected with 10⁵ CT26 tumor cells using hemispleen injection technique and then received no additional treatment (open diamond) or were administered 200 cGy of TBI (open square) on day 10 after surgery, 200 mg/kg of Cy intraperitoneally on day 13 (dark filled diamond), combination of TBI and Cy (dark filled square) or Cy followed by vaccine on day 16 (open circle). P < 0.005 for Cy vs. no treatment; P < 0.01 for no treatment vs. TBI, TBI + Cy vs. no treatment, and Cy vs. Cy + vaccine. b Intact IFN-γ-mediated T cell responses are necessary for preservation of Cy-mediated antitumor efficacy. i Experimental schema. ii BALB/c or IFN-γ^KO mice were injected with CT26 and left untreated (dark filled diamond—BALB/c; dark filled square—IFN-γ^KO) or Cy was administered (open diamond—BALB/c; open square—IFN-γ^KO) on day 13. P < 0.0001 for BALB/c no treatment vs. BALB/c Cy, IFN-γ^KO Cy, and IFN-γ^KO no treatment. c Depletion of CD4⁺ T cells does not affect Cy efficacy, while CD8⁺ T cell elimination completely eliminates Cy’s antitumor-effect. i Experimental schema. ii BALB/c mice were injected with CT26 and then treated intraperitoneally on days 6, 10, and 12 with 0.25 mg of IgG2b (dark filled diamond), anti-CD4 (open square), or anti-CD8 (dark filled square) and then injected with Cy on day 13 after tumor injection. P < 0.005 for Cy + isotype and Cy + anti-CD4 vs. Cy + anti-CD8. d Treg depletion after Cy administration does not improve survival of tumor-bearing animals. i Experimental schema. ii BALB/c mice were injected with CT26, and treated with Cy or left untreated. Animals then received 0.5 mg of anti-CD25 (open square—Cy treated; dark filled square—untreated) or isotype control (dark filled diamond—Cy treated; open diamond—untreated) on days 13 and 16 after tumor injection. P < 0.005 for Cy + isotype and Cy + anti-CD25 vs. isotype only and anti-CD25 only. In all experiments survival was monitored and is plotted as a function of time after tumor injection. Data are representative of at least three (a, b) or two (c, d) independent experiments