GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338087/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338087GEOGSEfalsePatient tumor bulk RNA-seq analysis of the pre-axi-cel treatment tumor microenvironment in large B cell lymphomaWe 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.2026/07/09GSE338087GSM9866371GSM9866360GSM9866370GSM9866373GSM9866362GSM9866361GSM9866372GSM9866383GSM9866379GSM9866368GSM9866367GSM9866359GSM9866369GSM9866364GSM9866375GSM9866374GSM9866363GSM9866366GSM986636524676338087Homo sapiens