Figure 5. Loss of Zeb1 in fibroblasts enables response to ICB therapy.

(A) Kaplan–Meier analysis showing tumor-free survival of Fib^Ctrl and Fib^ΔZeb1 mice after orthotopic transplantation of AKP^re organoids and intraperitoneal injection of anti-(a)-PD-L1 antibodies or control IgGs, as indicated by red arrows. Recombination of Zeb1 was induced by tamoxifen food starting from day (d) 3. Mice were considered tumor-free if no tumor was detected by palpation. Numbers of experimental mice per condition are indicated (Fib^Ctrl-ICB vs Fib^ΔZeb1-ICB: P = 0.0189, Mantel–Cox test). (B) Representative H&E images and quantification of tumor volumes after orthotopic transplantation of AKP^re tumor organoids and ICB. Only tumors collected after d28 were included in this analysis. Number of experimental mice per condition are indicated. IgG-treated mice contributed to the initial AKP^re analysis (Fib^Ctrl-ICB vs Fib^ΔZeb1-ICB: P = 0.0397, Fib^ΔZeb1-IgG vs Fib^ΔZeb1-ICB: P = 0.0792, Šídák’s multiple comparisons test). (C, D) ICB in the AOM/DSS model, applied by intraperitoneal injection of a-PD-L1 and a-CTLA-4 antibodies or control IgGs. Starting at d70 of AOM/DSS tumorigenesis antibodies were administered two times/week to all mice with at least 25–30% colon obstruction. This time point corresponds to d0 of ICB. Representative endoscopic images at d0 and d35 of ICB in the AOM/DSS model. Dotted line indicates unobstructed areas (C). Quantification of colon obstruction relative to d0 (D). Numbers of experimental mice per condition are indicated (Fib^Ctrl-ICB vs Fib^ΔZeb1-ICB: two-way ANOVA, day 35: P = 0.0211. Data information: Data are presented as mean ± SD (B) or mean ± SEM (D). Scale bars represent 1 mm (B). Source data are available online for this figure.