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. Author manuscript; available in PMC: 2020 Sep 15.

Published in final edited form as: Clin Cancer Res. 2019 Dec 23;26(6):1349–1358. doi: 10.1158/1078-0432.CCR-19-1068

Figure 4: — Anti-4-1BB + Anti PD-1 treatment efficacy correlates with 4-1BB expression on CD8⁺ TIL and not tumor histology or location. A. Survival curve of mice bearing IC CT2A, LLC, B16, or E0771 and treated with vehicle (control), anti-PD-1, anti-4-1BB, or the combination (n=8 per group). Mice were treated at day 9, 12, 15, and 18 with 200μg of each antibody via IP injection. *p<0.05, **p<0.01, ***p<0.001 by Log-rank (Mantel-Cox) Test. B. Survival curve of mice bearing IC LLC, B16, or E0771 and treated with vehicle (control) or anti-PD-1 and anti-4-1BB (n=8 per group). Mice were treated at day 3, 6, 9, 12, 15, and 18 with 200μg of each antibody via IP injection. *p<0.05, **p<0.01, ***p<0.001 by Log-rank (Mantel-Cox) Test. C. Frequency of CD8⁺ TIL expressing 4-1BB across different tumor types in untreated mice. Tumors were harvested when mice were moribund (day 15-20 after tumor implantation). ***p<0.001 by 1 way ANOVA followed by Bonferroni Multiple Comparison Test. D. Linear regression of 4-1BB levels on CD8⁺ TIL by the survival index, as measured by the ratio of median survival in mice treated with PD-1 and 4-1BB antibody to median survival in mice with tumor alone. p<0.09. E. Tumor growth curves of CT2A, LLC, B16, and E0771 implanted SC and subjected to the indicated treatments. Mice were sacrificed when tumors reached >2000mm³. 2-way ANOVA demonstrated significant effect of treatment in CT2A, B16, and E0771. *p<0.05, **p<0.01, ***p<0.001 by subsequent Bonferroni posttests. F. Frequency of CD8⁺ TIL expressing 4-1BB across IC and SC tumors. *p<0.05 by unpaired t-test.

Figure 4: — Anti-4-1BB + Anti PD-1 treatment efficacy correlates with 4-1BB expression on CD8⁺ TIL and not tumor histology or location. A. Survival curve of mice bearing IC CT2A, LLC, B16, or E0771 and treated with vehicle (control), anti-PD-1, anti-4-1BB, or the combination (n=8 per group). Mice were treated at day 9, 12, 15, and 18 with 200μg of each antibody via IP injection. *p<0.05, **p<0.01, ***p<0.001 by Log-rank (Mantel-Cox) Test. B. Survival curve of mice bearing IC LLC, B16, or E0771 and treated with vehicle (control) or anti-PD-1 and anti-4-1BB (n=8 per group). Mice were treated at day 3, 6, 9, 12, 15, and 18 with 200μg of each antibody via IP injection. *p<0.05, **p<0.01, ***p<0.001 by Log-rank (Mantel-Cox) Test. C. Frequency of CD8⁺ TIL expressing 4-1BB across different tumor types in untreated mice. Tumors were harvested when mice were moribund (day 15-20 after tumor implantation). ***p<0.001 by 1 way ANOVA followed by Bonferroni Multiple Comparison Test. D. Linear regression of 4-1BB levels on CD8⁺ TIL by the survival index, as measured by the ratio of median survival in mice treated with PD-1 and 4-1BB antibody to median survival in mice with tumor alone. p<0.09. E. Tumor growth curves of CT2A, LLC, B16, and E0771 implanted SC and subjected to the indicated treatments. Mice were sacrificed when tumors reached >2000mm³. 2-way ANOVA demonstrated significant effect of treatment in CT2A, B16, and E0771. *p<0.05, **p<0.01, ***p<0.001 by subsequent Bonferroni posttests. F. Frequency of CD8⁺ TIL expressing 4-1BB across IC and SC tumors. *p<0.05 by unpaired t-test.