{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE332nnn/GSE332885/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332885"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Multi-Organ Orchestration of the Hepatic and Immune Axis by Host MTDH Promotes Systemic Tumor Progression [ATAC-Seq]","description":"Cancer progression is systemically influenced by distant organ dysfunction induced by primary tumors, yet the mechanisms linking long distance tumor-organ crosstalk to antitumor immunity remain unclear. Here, we identify host Metadherin (MTDH) as a critical regulator of tumor-induced immunosuppression and metabolic reprogramming via tumor-liver interactions. Using Mtdh knockout (KO) mouse models, we show that concurrent MTDH loss in hepatocytes and CD8⁺ T cells enhances effector T cell function and suppresses tumor growth and metastasis. Mechanistically, tumor-derived extracellular vesicles (EVPs) activate Kupffer cells to secrete TNFα and TGF-β, which suppress hepatic PPARα-mediated lipid oxidation via NF-κB signaling. MTDH loss restores hepatic lipid catabolism and promotes mitochondrial metabolic reprogramming in CD8⁺ T cells in response to a lipid-reduced environment , thereby boosting anti-tumor immunity. Genetic or pharmacological targeting of MTDH synergizes with anti-PD-1 therapy in murine cancer models. These findings establish host MTDH as key modulator of tumor-liver crosstalk through metabolic and immune interactions, driving systemic cancer progression.","dates":{"publication":"2026/08/17"},"accession":"GSE332885","cross_references":{"GSM":["GSM9754601","GSM9754600"],"GPL":["24247"],"GSE":["332885"],"taxon":["Mus musculus"]}}