Abstract: TH-PO1147
High-Resolution Spatial Transcriptomics May Detect Micrometastasis from Renal Cell Carcinoma in "Normal"-Appearing Tissue
Session Information
- Onconephrology: Emerging Biomarkers, Preclinical Models, Clinical Challenges, and Therapeutic Strategies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Matsuura, Ryo, Johns Hopkins University, Baltimore, Maryland, United States
- Patel, Shishir Kumar, Johns Hopkins University, Baltimore, Maryland, United States
- Fallah Rastegar, Tara, Johns Hopkins University, Baltimore, Maryland, United States
- Noel, Sanjeev, Johns Hopkins University, Baltimore, Maryland, United States
- Allaf, Mohamad, Johns Hopkins University, Baltimore, Maryland, United States
- Fan, Jean, Johns Hopkins University, Baltimore, Maryland, United States
- Rabb, Hamid, Johns Hopkins University, Baltimore, Maryland, United States
Background
Detection of metastasis from renal cell carcinoma (RCC) is important to improve patient outcomes and currently performed with radiologic imaging or tissue histology. We hypothesized that advanced high resolution spatial transcriptomics (ST) (2mm x 2mm resolution, whole transcriptome) could detect micro-metastasis even when traditional approaches do not.
Methods
A patient with an 8 cm localized RCC had a total nephrectomy with clear margins and histologically normal adjacent kidney tissue. Two tissue sections were obtained from “normal” kidney regions remote from the tumor. These sections were analyzed with 10X Visium HD spatial transcriptomics. Data were processed for cell segmentation using bin2cell, cell type identification based on differentially expressed genes, niche clustering using BANKSY, and spatially-specific cell-cell communication analysis using LARIS.
Results
High-resolution ST of “normal” human kidney identified 14 kidney cell types including four immune cells (macrophages, dendritic cells, T cells and B cells) and 11 niches including glomeruli, parts of proximal and distal nephrons. One identified niche was notably enriched with immune cells, which accounted for nearly 50% of its composition. Thick ascending limb (TAL) in the immune cell-rich niche was characterized by high expression of WFDC2, ITGB8 and MIF, which are associated with RCC and poor response to immune checkpoint treatment (Cancer Cell 2021 PMID: 33711272). Cell-cell interaction analysis revealed that T cells interacted with TAL and fibroblasts via CXCL12-CXCR4 axis, and that TAL interacted with fibroblasts via COL3A1-ADGRG1 axis. Both ligand-receptor axes have been reported to be associated with cancer progression and metastasis (Front Immunol 2023 PMID: 38187400, Mol Biol Rep 2011 PMID: 20563655).
Conclusion
High-resolution ST revealed that “normal appearing” kidney tissue by imaging, direct visualization and histology distant from the RCC included immune cell-rich areas where epithelial cells had upregulated genes associated with carcinogenesis, poor response to ICI, and epithelial cells-immune cells -fibroblasts interactions. High resolution spatial transcriptomics may offer a new diagnostic tool for cancer micro-metastasis.
Funding
- NIDDK Support