(A–C) Intracellular GSH content indicated by mBBr staining was measured in splenic CD8⁺ cells and tumor-infiltrating CD8⁺ and CD45^– cells from LLC1-OVA–bearing mice. (D and E) Lipid ROS level indicated by BODIPY FITC was measured in splenic CD8⁺ cells and tumor-infiltrating CD8⁺ T cells from LLC1-OVA–bearing mice. (F–H) gpx4^fl/fl and gpx4^fl/fl CD4^cre OT-1 CD8⁺ T cells were activated in the presence of 10 ng/mL OVA-I and 1 μg/mL anti-CD28 with or without cell-permeable GSH, Lip-1, or a combination of both. On day 6, the percentages and/or numbers of viable (F), Ki67⁺ (G), and IFN-γ⁺ (H) T cells were measured. (I–K) gpx4^fl/fl and gpx4^fl/fl CD4^cre hosts were inoculated with MC38 tumor cells (n = 5). Tumor volume was measured twice a week (I). On day 21, the tumors were harvested, and tumor-infiltrating CD8⁺ T cells were counted (J) and evaluated for IFN-γ production by flow cytometry (K). (L) Tumor growth was measured in MC38-bearing gpx4^fl/fl and gpx4^fl/fl CD8^cre mice (n = 5). (M–O) Activated gpx4^fl/fl or gpx4^fl/fl CD4^cre OT-1 CD8⁺ T cells were transferred i.v. into EG7-bearing mice. Tumor growth (M) and survival (N) were measured (n = 3). Seven days after T cell transfer, tumor tissues were collected for detection of transferred OT-1 CD8⁺IFN-γ⁺ T cells (O). Results are representative of more than 3 (A–C and F–H) or 2 (D, E, I–K, and M–O) independent experiments. Data were analyzed by 2-tailed t test (B, C, E, J, K, and O), 2-way ANOVA (F–H, I, L, and M), and log-rank test for survival curves (N). Data plotted are mean ± SEM from biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.