a, Relative lipid ROS in B16 cells treated with supernatant from activated CD8+ T cells in the presence of anti-IFNγ or anti-TNF blocking antibody for 40 h. n = 4 biological replicates. ns, P = 0.1003, ****P < 0.0001 (one-way ANOVA). b, Relative lipid ROS in wild-type or IFNGR1−/− B16 cells treated with supernatant from activated CD8+ T cells for 40 h. n = 4 biological replicates. ns, P = 0.9981, **** P < 0.0001 (one-way ANOVA). c, Lipid ROS in B16 or HT-1080 cells treated with IFNγ for 24 h (representative histogram plot for fluorescence of oxidized BODIPY-C11). d, MFI of LiperFluo in B16 cells treated with IFNγ for 24 h. n = 4 biological replicates. ****P < 0.0001 (two-tailed t-test). e, MFI of LiperFluo in HT-1080 cells primed with IFNγ for 24 h, then treated with RSL3 (0.05 μM) for 6 h in the presence of Fer1 (10 μM). n = 4 biological replicates. **P = 0.0067, ***P = 0.0003, ****P < 0.0001 (two-way ANOVA). f, Relative lipid ROS of HT-1080 cells primed with IFNγ (10 ng ml−1) for 40 h and then treated with erastin (2 μM) for 8 h. n = 3 biological replicates. *P = 0.0426 or 0.0250 (one-way ANOVA). g, h, Relative viability of B16 (g) or HT-1080 (h) cells primed with or without (Ctrl) IFNγ for 40 h in the presence of Fer1 (10 μM), followed by treatment with different concentrations of erastin or RSL3 for 24 h. n = 3 or 4 biological replicates (mean ± s.d.). i, Percentage of 7-AAD+ cells among B16 cells primed with IFNγ (10 ng ml−1) for 40 h and then treated with RSL3 (0.1 μM) for 20 h. Representative images show cell death (left). n = 3 biological replicates. ****P < 0.0001 (one-way ANOVA). j, k, Percentage of 7-AAD+ cells among B16 (j) or HT-1080 (k) cells primed with IFNγ and then treated with RSL3 (0.1 μM, j) or erastin (4 μM, k) in the presence of Fer1(10 μM) or deferoxamine (DFO, 100 μM). n = 2 biological replicates. l, m, Relative content of oxygenated phosphatidylethanolamine (PE) (l) and phosphatidylcholine (PC) (m) species in HT-1080 cells primed with IFNγ (10 ng ml−1) for 48 h. n = 3 biological replicates. ***P = 0.0008, *P = 0.0167 (two-tailed t-test). n, Relative viability of HT-1080 cells primed with IFNγ for 24 h, then treated with ML162 (0.1 μM), ML210 (0.1 μM), or BSO (5 μM) for 24 h in the presence of Fer1 (10 μM). n = 3 (mean ± s.d.), ****P < 0.0001 (two-way ANOVA). o, Percentage of 7-AAD+ cells among HT-1080 cells primed with IFNγ, then treated with SAS (0.5 mM) for 40 h in the presence of Fer1 (10 μM). n = 2 biological replicates. p, Relative viability of B16 cells primed with IFNγ for 24 h, then treated with different concentrations of SAS for an additional 24 h. n = 3 (mean ± s.d.), ****P < 0.0001 (two-way ANOVA). q, Relative viability of HT-1080 cells primed with or without IFNγ, then cultured with medium supplemented with decreased concentrations of cystine in the presence of Fer1 (10 μM) for 20 h. n = 3 or 4 biological replicates (mean ± s.d.). r, Effect of IFNγ and SAS on HT-1080 tumour growth in vivo. HT-1080 cells (2 × 106 cells) were subcutaneously inoculated into NSG mice. Mice were treated either with IFNγ (1.5 × 105 U per mouse), SAS (120 mg/kg) or both. n = 5 animals in each group. *P < 0.05, ****P < 0.0001 (two-way ANOVA). Source data