biostudies-literatureUnknown16(1)Sun DThe treatment of gastric cancer remains challenging, with immunotherapy serving as a critical component of the holistic approach to its treatment. The results of this study indicated that statins could decrease the serum levels of interleukin-enhancing binding factor 3 (ILF3) and programmed cell death ligand 1(PD-L1) in GC patients and improve their prognosis. Functional experiments demonstrated that simvastatin induced ferroptosis by inhibiting ILF3 in GC cells and enhanced the killing effect of activated CD8⁺ T cells on GC cells. The CUT&Tag assay revealed that, mechanistically, simvastatin inhibited ILF3 expression by reducing the acetylation level at residue site H3K14 in ILF3. Next-generation sequencing and Kyoto Encyclopedia of Genes and Genomes analysis revealed that ILF3Cell death & disease208https://www.ebi.ac.uk/biostudies/studies/S-EPMC11947124biostudies-literatureSimvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells.PMC11947124Yang WWei MYan ZSun DCui XYu WZhang MfalseSimvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells.The treatment of gastric cancer remains challenging, with immunotherapy serving as a critical component of the holistic approach to its treatment. The results of this study indicated that statins could decrease the serum levels of interleukin-enhancing binding factor 3 (ILF3) and programmed cell death ligand 1(PD-L1) in GC patients and improve their prognosis. Functional experiments demonstrated that simvastatin induced ferroptosis by inhibiting ILF3 in GC cells and enhanced the killing effect of activated CD8⁺ T cells on GC cells. The CUT&Tag assay revealed that, mechanistically, simvastatin inhibited ILF3 expression by reducing the acetylation level at residue site H3K14 in ILF3. Next-generation sequencing and Kyoto Encyclopedia of Genes and Genomes analysis revealed that ILF32025-01-01T00:00:00Z2025 Mar2025-07-02T03:04:43.299Z2025-07-02T03:04:43.299ZS-EPMC119471244014064710.1038/s41419-025-07562-8