{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338087/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"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=GSE338087"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Patient tumor bulk RNA-seq analysis of the pre-axi-cel treatment tumor microenvironment in large B cell lymphoma","description":"We examined the tumor immune infiltrate and its relationship with clinical outcomes in patients with LBCL receiving Axicabtagene ciloleChimeric antigen receptor (CAR) T cell therapies have revolutionized B cell malignancy treatment, but many patients with large B cell lymphoma (LBCL) experience primary resistance or relapse. To uncover resistance mechanisms, we examined pre-infusion tumor biopsies and observed that increased immunoregulatory macrophages correlate with poor clinical responses. In murine models, CAR T cell-produced interferon-gamma (IFN-) upregulates inducible nitric oxide synthase (iNOS, NOS2) in immunoregulatory macrophages, impairing CAR T cell function. Proteomic profiling revealed that iNOS-expressing macrophages promote apoptosis and cell cycle arrest while downregulating protein synthesis machinery in CAR T cells. Metabolically, CAR T cells exhibit reduced glycolytic intermediates and altered tricarboxylic acid (TCA) cycle activity. Pharmacological inhibition of iNOS enhances CAR T cell treatment efficacy in vivo. Notably, elevated levels of iNOS+CD14+ monocytes in leukaphereses are associated with non-durable responses to CAR T cells. Targeting iNOS in immunoregulatory macrophages, potentially by modulating CAR T-produced IFN-, could improve LBCL outcomes.","dates":{"publication":"2026/07/09"},"accession":"GSE338087","cross_references":{"GSM":["GSM9866371","GSM9866360","GSM9866370","GSM9866373","GSM9866362","GSM9866361","GSM9866372","GSM9866383","GSM9866379","GSM9866368","GSM9866367","GSM9866359","GSM9866369","GSM9866364","GSM9866375","GSM9866374","GSM9866363","GSM9866366","GSM9866365"],"GPL":["24676"],"GSE":["338087"],"taxon":["Homo sapiens"]}}