{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326246/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326246"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Citraconate preserves T cell stemness and antitumor immunity","description":"Metabolic perturbations within the tumor microenvironment profoundly compromise the stem-like properties and functionality of CD8+ T cells. Elucidating the metabolic circuitry that maintains T cell stemness is therefore essential for rejuvenating tumor-infiltrating lymphocytes and enhancing immunotherapeutic efficacy. Here, we identify citraconate, an itaconate isomer, as a critical metabolite markedly depleted in CD8+ T cells under chronic antigen stimulation or hypoxia. Citraconate supplementation preserves stem-like properties, mitigates ferroptosis, and potentiates T cell-mediated antitumor efficacy. Mechanistically, citraconate sustains intracellular cAMP pool by suppressing phosphodiesterase (PDE1A/C) expression and maintaining mitochondrial integrity, thereby activating protein kinase A (PKA) signaling. This activation represses arachidonate-5-lipoxygenase (ALOX5) transcription, reducing arachidonic acid peroxidation. Clinically, reduced ALOX5 or PDE1A expression correlates with decreased T cell exhaustion and enhanced responses to immune checkpoint blockade (ICB) therapy. Our findings reveal the citraconate-mediated PDE1-cAMP-ALOX5 axis as a promising therapeutic target for potentiating cancer immunotherapy.","dates":{"publication":"2026/04/06"},"accession":"GSE326246","cross_references":{"GSM":["GSM9626133","GSM9642095","GSM9626132","GSM9626131","GSM9626130","GSM9626126","GSM9626129","GSM9626128","GSM9626127"],"GPL":["19057"],"GSE":["326246"],"taxon":["Mus musculus"]}}