Article Figures & Data
Figures
- Figure 1.
Augmented therapeutic effect and tumor rechallenge. A: Mice treated with the combination of monoclonal antibody to 4-1BB and to PD-1 had the best antitumor response, which resulted in complete tumor rejection in all mice injected with CT26 cells. Tumor volumes are shown as the mean±SE of five mice per group (*p<0.05, **p<0.01). Arrows, start of treatment. B: One hundred days after initial tumor inoculation, the surviving mice treated with anti-4-1BB and anti-PD-1 (referred to as immunized mice) were injected for a second time with 1×105 parental CT26 cells in the lower abdominal flank. Four nonimmunized (naïve) mice were injected in the same manner as a control group. Tumor volumes are the mean±SE. C: 4T1 cells were injected into both naïve (n=4) and immunized (n=4) mice. Mice from both groups developed tumors equivalently. Tumor volumes are the mean±SE.
- Figure 2.
CD4+ T-cells in the spleen after treatment. A: A significant increase in the number of CD4+ T-cells was observed in mice treated with any monoclonal antibody compared to naïve mice. B: A significant increase in the number of CD4+ IFN-γ+ T-cells was observed in the combination-therapy group. C: A significant increase in the number of CD4+ IL4+ T-cells was observed in the control and anti-PD-1-treated groups. Statistical significance was calculated by using one-way ANOVA with the Bonferroni post-hoc test (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001).
- Figure 3.
CD8+ T-cells in the spleen after treatment. A: A significant increase in the number of CD8+ T-cells was observed in mice treated with monoclonal antibody to 4-1BB alone and those treated with combination therapy. B: The mice treated with the combination therapy had most CD8+ IFN-γ+ T-cells. C: The mice treated with the combination therapy had an increased number of AH1-specific CD8+ T-cells. Statistical significance was calculated by using one-way ANOVA with the Bonferroni post-hoc test (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001).
- Figure 4.
Tregs and MDSCs in the LNs and spleen. The number of Tregs (A) and MDSCs (C) in the spleen was increased in mice treated with monoclonal antibody to 4-1BB mAb and combination therapy as compared with the other groups. The number of Tregs (B) and MDSCs (D) in the LN was the most increased in mice treated with anti-4-1BB. The number of Tregs and MDSCs are the average (±SE) number of cells derived from three mice. Statistical significance was calculated by using one-way ANOVA with the Bonferroni post-hoc test (*p<0.05, **p<0.01, ***p<0.001).
- Figure 5.
Pathological analysis of immune infiltration after therapy. Tumor-infiltrating T-cells were identified by immunohistochemical analysis on day 17 (A) and day 24 (B) after tumor inoculation. The presence of tumor-infiltrating T-cells was significantly increased on day 17 (C) and day 24 (D) after inoculation in mice treated with combination therapy. Tumor-infiltrating T-cells were counted at ×400 magnification. Photographs representative of three mice in each group are shown. Data are the mean±SE (*p<0.05; **p<0.01). Scale bar, 50 μm.
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