Fig. 1: Competitive uptake of cystine by tumor cells leads to T-cell exhaustion and death.

a Analysis of the correlation between immune infiltration and SLC7A11 expression in tumors via TIMER 2.0 database. b Slc7a11 mRNA expression in CD8⁺ T effector cells and tumor cells (n = 3 per group). c CD8⁺ T, B16F10, and MC38 cells were cultured with varying cystine concentrations, and cell viability was detected by CCK8 assay (n = 3 per group, CD8⁺ T EC50 = 18.05, B16F10 EC50 = 0.1444, MC38 EC50 = 5.326). d CD8⁺ T cells and B16F10 cells were co-cultured at 1:1 for 24 h in NM and CD, and cell viability was detected by CCK8 assay (n = 3 per group). e CD8⁺ T cells were cultured for 24 h in fresh medium or B16F10 cell supernatant with varying cystine concentrations, and the percentages of dead cells were detected by flow cytometry (n = 3 per group). f–m Effects of prolonged cystine starvation on CD8⁺ T-cell differentiation and death. T cells were cultured in NM or CD for 72 h (n = 3 per group), and the percentages of dead cells (f), PD-1⁺TIM-3⁺ subset (g), CD62L⁺CD44⁺ subset (h), LY108⁺TIM-3^- subset (i), and the levels of TCF1 (j) and TOX (k) were detected by flow cytometry. IFNγ, TNFα (l), and IL-2 (m) secretion was measured after re-stimulation. Each symbol represents one individual. Data are presented as mean ± s.e.m. p values are measured by two-tailed unpaired Student’s t test (b, f–m) and one-way ANOVA with Tukey’s multiple comparison test (d, e). *p < 0.05, **p < 0.01, ***p < 0.001.