{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE346nnn/GSE346776/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346776"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Arginine Rewires eIF4F Translation Initiation to Overcome Fever-Induced CAR T-Cell Dysfunction","description":"Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of hematological malignancies, but cytokine release syndrome (CRS) remains a major toxicity. Fever—a hallmark of CRS—has been understudied as a modifier of therapeutic efficacy. In a retrospective cohort of patients with B-cell acute lymphoblastic leukemia treated with CD22-directed CAR T-cells (NCT02315612), sustained high-grade fever inversely correlated with clinical response. Mechanistically, experimental hyperthermia impaired proximal CAR signaling, reduced cytotoxicity, and compromised metabolic fitness through dysregulated arginine metabolism. Arginine supplementation restored CAR T-cell function following hyperthermic stress and enhanced cytotoxicity under normothermic conditions. This effect required mTOR-dependent recruitment of the eIF4F translation initiation complex and downstream cMYC-driven metabolic reprogramming. Importantly, arginine enhanced GMP-manufactured CAR T-cell function under normothermia, while oral supplementation improved in vivo efficacy. These findings identify metabolic control of translation as a fever-sensitive checkpoint and establish arginine supplementation as a tractable strategy to enhance CAR T-cell efficacy.","dates":{"publication":"2026/09/14"},"accession":"GSE346776","cross_references":{"GSM":["GSM10040274","GSM10040273","GSM10040272","GSM10040271","GSM10040267","GSM10040266","GSM10040276","GSM10040265","GSM10040275","GSM10040269","GSM10040268","GSM10040270"],"GPL":["30173"],"GSE":["346776"],"taxon":["Homo sapiens"]}}