Fig. 3: Impaired abscopal effect in previously irradiated mice is restored by ABT263.
From: Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

a Schematic of the experiment. CTL or TBI mice treated or not with ABT263 were inoculated on each flank with 3 or 5 × 105 MC38 tumor cells. On days 12, 13, and 14 after tumor inoculation, the larger primary tumor was exposed to 3 rounds (8 Gy each) of radiotherapy (RT). Mice were then injected on days 14, 17, and 20 with a αCTLA-4 blocking antibody and tumor growth evaluated until reaching a limit point. Alternatively, some mice were euthanized at day 22 and tumors surgically removed to allow immune infiltration analysis. b Tumor growth was evaluated for each of the indicated groups of mice. Each line represents the growth of an individual tumor over 28 days or until the mouse had to be removed from the study. The total number of tumors per group is indicated in parenthesis. 2way ANOVA with Tukey correction. Shown is the mean ± SEM. c Kaplan–Meyer survival plots for each of the indicated conditions. d Histogram showing the proportion of mice in each group achieving complete secondary (abscopal) tumor elimination (CE). e Shown is the weight of the secondary tumors at day 22 prior to dissociation. n = 29 CTL, n = 17 CTL (RT + αCTLA4), n = 15 CTL + ABT263, n = 5 CTL + ABT263 (RT + αCTLA4), n = 29 TBI, n = 19 TBI (RT + αCTLA4), n = 16 TBI + ABT263, n = 19 TBI + ABT263 (RT + αCTLA4) tumor from independent animals. Brown-Forsythe and Welch ANOVA test with Games-Howell correction. Shown is the mean ± SEM. f Tumor immune cells infiltration as determined by flow cytometry from dissociated tumors on day 22 post inoculation. Shown are the proportions of CD8 T cells, CD4 T cells and CD11b+ cells over the total number of CD45+ cells collected from tumors. For CD8 and CD4, n = 29 CTL, n = 17 CTL (RT + αCTLA4), n = 5 CTL + ABT263, n = 5 CTL + ABT263 (RT + αCTLA4), n = 24 TBI, n = 17 TBI (RT + αCTLA4), n = 16 TBI + ABT263, n = 18 TBI + ABT263 (RT + αCTLA4) tumors from independent animals. For CD11b, n = 20 CTL, n = 9 CTL (RT + αCTLA4), n = 5 CTL + ABT263, n = 5 CTL + ABT263 (RT + αCTLA4), n = 18 TBI, n = 10 TBI (RT + αCTLA4), n = 12 TBI + ABT263, n = 11 TBI + ABT263 (RT + αCTLA4) tumors from independent animals. Ordinary one-way ANOVA with Tukey correction. Shown is the mean ± SEM. g Shown is the ratio of CD8 T cells over CD11b+ cells in tumors at day 22. n = 20 CTL, n = 9 CTL (RT + αCTLA4), n = 5 CTL + ABT263, n = 5 CTL + ABT263 (RT + αCTLA4), n = 18 TBI, n = 10 TBI (RT + αCTLA4), n = 12 TBI + ABT263, n = 11 TBI + ABT263 (RT + αCTLA4) tumors from independent animals. Brown-Forsythe and Welch ANOVA with Games-Howell correction. Shown is the mean ± SEM. h Shown is the quantification of the expression of IFNγ as measured by flow cytometry in infiltrated CD8 T cells at day 22. n = 4 CTL, n = 8 CTL (RT + αCTLA4), n = 4 CTL + ABT263, n = 4 CTL + ABT263 (RT + αCTLA4), n = 4 TBI, n = 8 TBI (RT + αCTLA4), n = 4 TBI + ABT263, n = 8 TBI + ABT263 (RT + αCTLA4) tumors from independent animals. Ordinary one-way ANOVA with Tukey correction. Shown is the mean ± SEM. Source data are provided as a Source Data file.