Tumor cell-expressed PD-L1 reprograms lipid metabolism via EGFR/ITGB4/SREBP1c signaling in liver cancer

•Tumor cell-expressed PD-L1 drives lipid metabolism reprogramming in tumors.•PD-L1 forms a complex with EGFR/ITGB4 to trigger lipid metabolism reprogramming in HCC.•PD-L1 triggers lipid metabolism reprogramming via driving EGFR/ITGB4/PI3K/Akt/mTOR/SREBP1c/FASN/ACLY signaling in tumors.•PD-L1-mediated lipid metabolism reprogramming supports the tumor growth in vitro and in vivo.•The anti-PD-L1 antibody might release the resistance of anti-EGFR antibody cetuximab in clinic.