Tumor-stromal crosstalk and macrophage enrichment is associated with chemotherapy response in bladder cancer
This dataset provides a spatial transcriptomic atlas of bladder cancer tissue treated ex vivo with standard chemotherapy. Tumor specimens from eight bladder cancer patients were excised and treated for 48 hours with gemcitabine and cisplatin (GemCis) or medium control (MSC), followed by formalin fixation and paraffin embedding. Spatial gene expression profiling was performed using the NanoString GeoMx Digital Spatial Profiler Whole Transcriptome Atlas (WTA), capturing expression of over 18,000 transcripts. Tumor regions were identified by cytokeratin (CK) staining and analyzed alongside adjacent stroma (CK-negative). Chemotherapy treatment led to significant transcriptomic alterations, including downregulation of pathways related to substance uptake (e.g., endocytosis) and metabolism (e.g., glycolysis), and upregulation of cell death pathways. Cellular deconvolution using xCell revealed stromal M2 macrophage enrichment in chemotherapy-resistant samples, suggesting a microenvironmental contribution to resistance. Overall design: Fresh tumor tissue from eight patients with bladder cancer was obtained and divided into two conditions: treatment with gemcitabine/cisplatin (GemCis) or medium control (MSC), incubated for 48 hours ex vivo. Post-treatment, tissues were formalin-fixed, paraffin-embedded, and processed using the NanoString GeoMx DSP Whole Transcriptome Atlas (WTA) assay. Regions of interest (ROIs) were selected based on immunohistochemical cytokeratin (CK) staining to distinguish tumor cells (CK-positive) from stroma (CK-negative). Two technical replicates per condition and region were collected. Standard GeoMx WTA workflow was applied, with downstream analysis including differential expression, pathway analysis, caspase-3 immunohistochemistry for treatment response classification, and xCell-based deconvolution to profile immune cell populations. The resulting data provide spatial resolution of transcriptomic changes in response to chemotherapy and insights into mechanisms of chemoresistance in bladder cancer.