(A and B) GPX4 expression level was evaluated by flow cytometry in activated WT and adora2a^fl/fl Lck^cre cKO CD8⁺ T cells. (C) ATAC-seq analysis by Partek Flow software showing chromatin accessibility within the vicinity of transcribed regions for GPX4 in activated Pmel CD8⁺ T cells treated with or without A2ARi. (D) Predicted binding sites by PROMO-ALGGEN Web tool for human and mouse gpx4 by E2F1. (E) Correlation between gene expression levels of e2f1 and gpx4 by qRT-PCR in activated Pmel CD8⁺ T cells. (F and G) qRT-PCR was performed to detect expression levels of e2f1 in activated Pmel CD8⁺ T cells treated with or without A2ARi (F) or with or without H89 (G). (H) ATAC-seq analysis by Partek Flow showing chromatin accessibility within the vicinity of transcribed regions for E2F1 in activated Pmel CD8⁺ T cells treated with or without A2ARi. (I) ChIP-qPCR analysis confirming the binding capacity of E2F1 on gpx4 in activated control OT-1 CD8⁺ T cells rather than gpx4^fl/fl CD4^cre OT-1 CD8⁺ T cells. (J–L) Activated Pmel CD8⁺ T cells in the presence of gp100, anti-CD28, 5′-AMP, and cell-permeable GSH were treated with or without A2ARi, Lip-1, E2F1 inhibitor HLM 006474, or combination. On day 7, the percentages of viable (J), Ki67⁺ (K), and IFN-γ⁺ (L) T cells were measured. Results are representative of 2 (C, H, and I) or 3 (B, E–G, and J–L) independent experiments. Data were analyzed by Pearson’s correlation (E), 2-tailed t test (B, F, and G), and 2-way ANOVA (I–L). Data plotted are mean ± SEM from biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.