Extended Data Fig. 5: Unnecessary fatty acid uptake boosts FAO dysfunction in TME CD8⁺ T cells.

(A) MFI of lipid radical, acrolein and PC-Acro in naïve (CD62L^high CD44^low) CD8⁺ T cells in PBMCs from Hadha^flox/flox (Ctrl) and Hadha^flox/flox Cd4-Cre (KO) male mice (Ctrl, n = 7 mice; KO, n = 5 mice). (B) MFI of pAkt, pS6 and 2-NBDG in naïve CD8⁺ T cells in PBMCs from Ctrl and KO male mice (Ctrl, n = 7 mice; KO, n = 5 mice). (C) CD36 expression and BODIPY C₅, C₁₂, and C₁₆ (fatty acid uptake) in naïve CD8⁺ T cells in PBMCs from Ctrl and KO male mice. (Ctrl, n = 7 mice; KO, n = 5 mice). (D) BODIPY C₅, C₁₂, and C₁₆ in Tim-3⁻ and Tim-3⁺ populations among PD-1⁺ CD8⁺ T cells in MC38 tumors on day 14 (n = 5 mice). (E) The positive loop toward intensive oxidative stress by FAO dysfunction in CD8⁺ T cells in TME. Acrolein production following lipid peroxidation damages mitochondria and reduces the FAO activity. FAO dysregulation promotes fatty acid uptake and drives further accumulation of lipid peroxidation and acrolein. Created with BioRender.com, elements adapted and assembled using PowerPoint. Data are means ± SEMs (A to C). P values were determined using unpaired two-tailed Student’s t tests (A to C) or paired two-tailed Student’s t tests (D). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Data are representative of two independent experiments with similar results.