Fig. 8: The antitumor effects of IFN-γ on WT tumor cells drives selection for IFNγR2-mutant tumor cells.

a and b Correlation between the concentration of intratumoral IFN-γ and the fold-change in the frequency of BFP⁺ versus ZsGreen⁺ tumor cells (a) and the total number of H-2K^b/SIY⁺ CD8⁺ TILs (b). c Correlation between the total number of H-2K^b/SIY⁺ CD8⁺ TILs and fold-change in the frequency of BFP⁺ versus ZsGreen⁺ tumor cells. a–c Tumors were analyzed on day 14 after tumor inoculation. All data were log2-transformed. n = 60 mice (a, c) and n = 49 mice (b); data are pooled from five independent experiments. d Concentration of IFN-γ after CD8⁺ T cell depletion. n = 35 mice (no treatment) and n = 15 mice (anti-CD8α) e Correlation between intratumoral IFN-γ and log₂(BFP/ZsGreen) fold-change in the absence of CD8⁺ T cells. Mice received 200 μg anti-CD8a (clone YTS169.4) on days -1 and 7. Tumors were analyzed on day 14. n = 10 mice; data are pooled from two independent experiments. f Fold-change in BFP⁺ versus ZsGreen⁺ tumor cells after administration of recombinant mouse IFN-γ. 50 μg of IFN-γ was administered i.p. on days 7, 10, 13, and 16. Tumor cell composition was analyzed on day 18. n = 10 mice (WT:WT and WT:WT + IFN-γ), n = 12 mice (WT:IγR2), and n = 15 mice (WT:IγR2 + IFN-γ); data are pooled from two independent experiments. g Tumor outgrowth of mixed WT and PD-L1-mutant tumors. n = 10 mice; data are pooled from two independent experiments. Results are expressed as mean ± s.e.m. Least squares regression was performed in (a–c, e). Statistical significance was determined by a Mann-Whitney test (f) and a two-way ANOVA Bonferroni post-hoc test (g). *p < 0.05, **p < 0.01, ***p < 0.001.