GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335399/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335399GEOGSEfalseDimethyl Fumarate Reprograms Liver Cancer Immunity via NF-κB/PD-L1 Suppression and Cuproptosis Induction: A Novel Therapeutic StrategyBackground: Dimethyl fumarate (DMF) possesses immunoregulatory and anti-tumor properties, yet its therapeutic potential in liver cancer remains unexplored. This study aimed to investigate DMF’s role in liver cancer immune regulation and elucidate the underlying molecular mechanisms. Methods: Cell viability, proliferation, and cell cycle were assessed using CCK-8, colony formation, and flow cytometry. NF-κB signaling, cuproptosis-related proteins, and PD-L1 were analyzed by Western blot. Aerobic glycolysis and Oxidative phosphorylation were evaluated via ECAR, OCR, lactate production, glucose consumption, and GAPDH activity. PD-L1, HSP70, and DLAT aggregation were quantified by immunofluorescence. The combined anti-tumor efficacy of DMF and cuproptosis induction was validated in a murine liver cancer model. Results: DMF suppressed liver cancer cell viability, clonogenicity, and cell cycle progression while downregulating PD-L1 expression through NF-κB pathway inhibition. It attenuated aerobic glycolysis and promoted cuproptosis. In tumor-immune cell co-cultures, DMF enhanced dendritic cell and natural killer cell function by dual-targeting NF-κB/PD-L1 and inducing cuproptosis. In vivo, DMF combined with Cu-ES increased immune cell infiltration and significantly inhibited tumor progression. Conclusion: DMF combined with cuproptosis induction remodels the tumor immune microenvironment and represents a novel therapeutic strategy to potentiate immunotherapy efficacy in liver cancer.2026/10/01GSE335399GSM9812864GSM9812863GSM9812866GSM9812865GSM9812860GSM9812870GSM9812862GSM9812861GSM9812868GSM9812867GSM9812859GSM981286911154335399Homo sapiens