{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293952/"]},"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=GSE293952"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma [bulk RNA-seq]","description":"Vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors (VEGFR-TKIs) and aPD1 combinations are effective in multiple solid tumors, particularly in clear cell renal cell carcinoma (ccRCC), due it’s characteristic pseudo-hypoxic, hyper-angiogenic state driven by biallelic VHL-loss. However, long-term durability is inferior to dual aPD1/aCTLA4 regimens, yet the mechanisms underlying these differences remain unclear. Since tumor-associated macrophages (TAMs) are implicated in therapeutic resistance, we used scRNAseq to investigate TAM evolution following VEGFR-TKI, aPD1 and combined VEGFR-TKI/aPD1 treatment in a transgenic ccRCC mouse model. We identify hypoxia-responsive SPP1+ TAMs that are absent in baseline pseudo-hypoxic tumors. This proxy of true hypoxia tracks with successful response to VEGFR-TKI/aPD1 in mouse and human on-treatment samples, reflecting treatment-induced hypoxic necrosis. Paradoxically, pretreatment hypoxia predicted worse outcomes across multiple VEGFR-TKI/aPD1 trial and real-world cohorts and extended exposure to hypoxia-inducing VEGFR-TKIs and aPD1 exacerbated metastasis in mice, highlighting the dual implications of hypoxia in ccRCC disease trajectory.","dates":{"publication":"2026/04/23"},"accession":"GSE293952","cross_references":{"GSM":["GSM8895152","GSM8895151","GSM8895110","GSM8895154","GSM8895153","GSM8895112","GSM8895156","GSM8895155","GSM8895111","GSM8895158","GSM8895114","GSM8895113","GSM8895157","GSM8895116","GSM8895115","GSM8895159","GSM8895117","GSM8895119","GSM8895150","GSM8895141","GSM8895140","GSM8895143","GSM8895142","GSM8895145","GSM8895144","GSM8895147","GSM8895146","GSM8895105","GSM8895149","GSM8895104","GSM8895148","GSM8895107","GSM8895106","GSM8895109","GSM8895108","GSM8895130","GSM8895132","GSM8895131","GSM8895134","GSM8895133","GSM8895136","GSM8895135","GSM8895138","GSM8895137","GSM8895139","GSM8895163","GSM8895162","GSM8895121","GSM8895165","GSM8895164","GSM8895167","GSM8895123","GSM8895166","GSM8895125","GSM8895124","GSM8895127","GSM8895126","GSM8895129","GSM8895128","GSM8895161","GSM8895160"],"GPL":["24676"],"GSE":["293952"],"taxon":["Homo sapiens"]}}