Effects of combinations of immunotherapy agents on the multifocal HCC model and bioluminescence follow-up of the tumors
(A) Mice bearing multifocal HCC following hydrodynamic injection were treated at weekly intervals with anti-PD-1, anti-CTLA-4, or a combination of the two checkpoint inhibitors.
(B) Bioluminescence images on days 32 and 64 and their quantification. Medians and 95% CI are shown.
(C) Survival of the experimental groups of mice.
(D) Similar scheme of treatments but testing triplet combinations including anti-PD-1 + anti-CTLA-4 + anti-CD137 and anti-PD-1 + anti-CTLA-4 + IL-2 starting on day 7. IL-2 was given in 3-day cycles dosed every 12 h as indicated.
(E) Bioluminescence images on day 32 and 64 to monitor tumor burden. Medians and 95% CI are shown
(F) Survival of the experimental groups of mice.
(G) Similar experiments postponing treatment onset to day 21.
(H) Bioluminescence imaging. Images with a crossed rectangle represent dead mice at the time of bioluminescence imaging.
(I) Overall survival. Number of mice and median overall survival are provided.
(J) Individual tumor size follow-up of the groups of mice given the indicated treatments. Statistical comparisons were made using Kruskal-Wallis, repeated measures ANOVA, followed by Tukey’s test calculated with logarithmic data transformation and log rank (Mantel-Cox) test. All experiments were repeated at least twice. See also Figures S4 and S5.