ArticleGenome biology2024
Increased spatial coupling of integrin and collagen IV in the immunoresistant clear-cell renal-cell carcinoma tumor microenvironment.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Spatial Autocorrelation Aware Resampling Improves Cell-Cell Interaction Inference in Spatial Transcriptomics Data.bioRxiv : the preprint server for biology · 2026Article
- Spatial Immunology in Translation: Linking Immune Organisation to Therapeutic Outcome.Medical sciences (Basel, Switzerland) · 2026Review
- An orally bioavailable pan-αv/α5β1 integrin antagonist prevents aggressive prostate cancer progression via suppressing both oncogenic signals and CD47-mediated immune escape.Molecular cancer · 2026Article
- Single-cell profiling of bone metastasis ecosystems reveals pivotal role of INSRTranslational oncology · 2026Article
- Single-cell spatial transcriptomics uncovers niches that govern response to PD-1/PD-L1 blockade in cutaneous squamous cell carcinoma.Journal for immunotherapy of cancer · 2026Article
- Why CAR T cell therapy fails in renal cell carcinoma.Frontiers in immunology · 2026Review
- Tumor-associated neutrophils in renal cell carcinoma.Frontiers in immunology · 2026Review
- FastPCA: An R package for fast singular value decomposition.Journal of open source software · 2026Article
- Astragaloside IV regulates macrophage polarization via the TLR4/NF-κB/STAT3 pathway to inhibit the malignant phenotype of renal clear cell carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Lessons learned from spatial transcriptomic analyses in clear-cell renal cell carcinoma.Nature reviews. Urology · 2025Review
- FAPNature communications · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- scSpatialSIM: a simulator of spatial single-cell molecular data.SoftwareX · 2025Article
- Mendelian randomization and single-cell analysis reveal causal relationships between renal clear cell carcinoma, kidney fibrosis, and inflammatory factors.Discover oncology · 2025Article
- Cancer therapy resistance from a spatial-omics perspective.Clinical and translational medicine · 2025Review
- Spatial and genomic profiling of residual breast cancer after neoadjuvant chemotherapy unveil divergent fates for each breast cancer subtype.Cell reports. Medicine · 2025Article
- Quantifying and interpreting biologically meaningful spatial signatures within tumor microenvironments.NPJ precision oncology · 2025Review
- CSF2 polarized neutrophils and invaded renal cancer cellsOpen medicine (Warsaw, Poland) · 2025Article
- Prognostic biomarker and clinical significance of PLOD gene family in clear cell renal cell carcinoma.Frontiers in oncology · 2025Article
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Abstract
backgroundImmunotherapy has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with immunotherapy naïve and exposed primary ccRCC tumors to better understand immunotherapy resistance.
resultsSpatial molecular imaging of tumor and adjacent stroma samples from 21 tumors suggests that viable tumors following immunotherapy harbor more stromal CD8 + T cells and neutrophils than immunotherapy naïve tumors. YES1 is significantly upregulated in immunotherapy exposed tumor cells. Spatial GSEA shows that the epithelial-mesenchymal transition pathway is spatially enriched and the associated ligand-receptor transcript pair COL4A1-ITGAV has significantly higher autocorrelation in the stroma after exposure to immunotherapy. More integrin αV + cells are observed in immunotherapy exposed stroma on multiplex immunofluorescence validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both COL4A1 and ITGAV. Assessing bulk RNA expression and proteomic correlates in CPTAC databases reveals that collagen IV protein is more abundant in advanced stages of disease.
conclusionsSpatial transcriptomics of samples of 3 patient cohorts with cRCC tumors indicates that COL4A1 and ITGAV are more autocorrelated in immunotherapy-exposed stroma compared to immunotherapy-naïve tumors, with high expression among fibroblasts, tumor cells, and endothelium. Further research is needed to understand changes in the ccRCC tumor immune microenvironment and explore potential therapeutic role of integrin after immunotherapy treatment.
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