Figure 1. Ezetimibe enhances lymphocyte function to inhibit tumor growth and metastasis in mice.

A. Mice were treated with ezetimibe for 14 days prior to subcutaneous injection of syngeneic tumor cell lines. B. B16 melanoma cells were injected into B6 mice (8-9 mice/group) C. RM1 prostate adenocarcinoma cells were injected into B6 mice (9-10 mice/group). D. RENCA renal cell carcinoma cells were injected into Balb/c mice (5-6 mice/group). In each experiment, one group received ezetimibe and depleting αCD8 antibody two days after s.c. tumor injection into the flank. P-values were obtained by using the repeated measures ANOVA (A-D). E. To determine if immunity is lymphocyte-dependent, mice were treated with ezetimibe for 14 days to lower cholesterol and then vaccinated with DCs pulsed with B16 tumor lysate. Spleen and lymph nodes were harvested from these mice, and CD8+ cells were isolated and cultured in vitro with tumor lysate pulsed DC and IL-2 for 3 days. 2x10⁶ activated CD8+ cells were adoptively transferred by tail vein injection into recipient mice, which were challenged with i.v. B16 cells. Lung tumors were examined 25 days later. F. Representative lungs are shown from recipient mice, labeled with the donor mouse treatment. G. Lung weights (top) and CD8+ T cell IFN-γ response to ex vivo restimulation (bottom) are shown. Graphs are labeled with the treatment provided to the donor mice. H. In a similar experiment, B6 mice were treated with DCs pulsed with RM1 tumor lysate. Lymphocytes were transferred into recipient mice that were challenged with i.v. RM1 cells. I. Representative H&E sections of lungs from each treatment group are shown. J. Lung weights (top) and tumor number in the lungs (bottom) are shown. Each group contained 3 mice. Each experiment was conducted at least twice to confirm results (B,C,E-J). Error bars represent standard error.