Fig. 5: IFNI mediates the effect of ceralasertib in tumor microenvironment.

a TGR of CT26 tumors in mice treated with ceralasertib 7 days-on/7 days-off and with an IFNAR1 blocking antibody b.i.w. Values for individual mice (N = 10), median, and min-max values are shown. Statistical analysis was performed using one-way ANOVA corrected for multiple comparisons. Box-whisker plots shows individual tumors, median and min-max values. NS—non-significant (p > 0.05). b WT or IFNAR1 KO BM cells were transferred to congenic lethally irradiated mice. After 8 weeks mice were implanted with MC38 tumor cells and treated with ceralasertib (6.25 mg/kg b.i.d.) with or without anti-PD-L1 (10 mg/kg b.i.w.). TGR for individual mice, median, and min-max are shown. n = 8 per group. Statistical analysis was performed with one-way ANOVA corrected for multiple comparisons. P values are shown on graphs. NS—non-significant (p > 0.05). c CD4⁺ and CD8⁺ T cells were isolated from spleens of naïve mice, treated for 72 h with indicated concentration of IFN-β in the presence of CD3/CD28 antibodies. Expression of PD1 was measured by flow cytometry. Individual results (N = 3), mean and SEM are shown. P values were calculated in One-way ANOVA with correction for multiple comparisons and shown on graphs were possible to maintain readability of the graphs **p < 0.01; ***p < 0.001. The same results were obtained after 48 h of treatment. d IFNAR1 KO (N = 6) MC38 TB mice treated for 7 days with ceralasertib as described for WT mice (Fig. S8C). Expression of PD1 was measured by flow cytometry in spleen and tumor CD4⁺ and CD8⁺ T cells and P values were calculated in two^-sided unpaired Student’s t-test. Individual mice results (N = 6), mean and SEM are shown. e Tumor volume in mice reconstituted with BM from WT or IFNAR1^SA mice and implanted 8 weeks later with MC38 tumor cells. Mice treated with 6.25 mg/kg ceralasertib for 7 days. N = 10 per group. Statistical analysis performed by Fishers test. Source data are provided as a Source Data file.