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. Author manuscript; available in PMC: 2019 Nov 1.
Published in final edited form as: Nature. 2019 May 1;569(7755):270–274. doi: 10.1038/s41586-019-1170-y

Figure 2. IFNγ sensitizes tumor cells to ferroptosis by inhibiting system xc-.

Figure 2

a, b, Relative lipid ROS (a) or the percentage of 7-AAD+ dead cells (b) in OVA-pulsed wild-type or IFNGR1 deficient (IFNGR1−/−) B16 cells co-cultured with OT-I cells (B16: OT-I = 1: 1) for 24 hours followed by treatment with RSL3 (0.1 μM) for additional 20 hours. n = 3 biological replicates. In a, ** P = 0.0012; *** P = 0.0001; ns, P = 0.9995 and 0.4244 were determined by one-way ANOVA. In b, **** P < 0.0001; ns, P = 0.2306 and 0.7842 were determined by one-way ANOVA.

c, Relative lipid ROS of B16 cells primed by IFNγ (10 ng/ml) for 40 hours and followed with erastin (1 μM) or RSL3 (0.1 μM) treatment for 8 hours. n = 2 biological replicates.

d, The percentage of 7-AAD+ HT-1080 cells primed by IFNγ (10 ng/ml) for 40 hours and followed with erastin (4 μM) or RSL3 (0.05 μM) for 20 hours. n = 2 or 3 biological replicates; **** P < 0.0001 as determined by one-way ANOVA.

e, Relative content of oxygenated PC species in HT-1080 cells primed by IFNγ for 40 hours and followed with RSL3 (0.01 μM) for 10 hours. n = 3 biological replicates; ** P = 0.0016; *** P = 0.0001; * P = 0.0440 and * P = 0.0325 were determined by one-way ANOVA.

f, Tumor growth in HT-1080 tumor-bearing NSG mice that were treated with PBS (n = 9), IFNγ (n = 11), liproxstatin-1 (n = 12) or IFNγ plus liproxstatin-1 (n = 11). **** P < 0.0001 as determined by two-way ANOVA.

g, Immunoblots of SLC7A11, SLC3A2, and IRF1 in HT-1080 cells treated with IFNγ (10 ng/ml) for 24 hours. β-actin serves as the loading control. Images are representative of three experiments.

h, 14C-Cystine content in IFNγ-treated HT-1080 cells incubated in 14C-Cystine supplemented medium for 45 minutes. n = 3 or 4 biological replicates; **** P < 0.0001 as determined by two-tailed t-test.

i, The percentage of 7-AAD+ dead cells in HT-1080 expressing scramble shRNA or 3 individual shRNA targeting SLC7A11 (shSLC7A11–1, 2, 3) treated with different concentrations of erastin for 24 hours. One of 3 repeats is shown.