{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309615/"]},"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=GSE309615"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Sphingosine Kinase-2 Inhibition Increases Acetyl-CoA Carboxylase Activity and Phosphatidylcholine Levels to Program Immunogenicity in Myeloid-Derived Suppressor Cells [ATAC-seq]","description":"Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) are a major barrier to adoptive T cell therapy, underscoring the need to enhance T cell efficacy by overcoming immunosuppression. Here, we investigated how sphingosine-1-phosphate (S1P), an abundant signaling lipid in the TME, regulates the programming and function of MDSCs. We show that inhibition of sphingosine kinase-2 (SphK2), which generates S1P in MDSCs, reduces their suppressive activity and enhances antigen presentation. Pharmacological inhibition of SphK2 improved the response to anti-PD1 therapy in preclinical models of checkpoint-resistant breast, bladder, and melanoma cancers by mitigating MDSCmediated suppression, thereby limiting tumor progression. Mechanistically, S1P directly interacts with Acetyl-CoA Carboxylase 1 (ACC1) to inhibit its activity, altering fatty acid and glycolytic pathways. Lowering intracellular S1P restores ACC activity and promotes phosphatidylcholine synthesis, reducing the immunosuppressive phenotype of MDSCs. These findings highlight the SphK2/ACC/phospholipid axis as a promising therapeutic target in cancer immunotherapy.","dates":{"publication":"2026/05/04"},"accession":"GSE309615","cross_references":{"GSM":["GSM9270502","GSM9270503","GSM9270500","GSM9270501"],"GPL":["24247"],"GSE":["309615"],"taxon":["Mus musculus"]}}