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FAP+ fibroblasts orchestrate tumor microenvironment remodeling in renal cell carcinoma with tumor thrombus
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FAP+ fibroblasts orchestrate tumor microenvironment remodeling in renal cell carcinoma with tumor thrombus
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Journal Article
FAP+ fibroblasts orchestrate tumor microenvironment remodeling in renal cell carcinoma with tumor thrombus
2025
Overview
Tumor thrombus (TT) worsens prognosis and complicates surgery in renal cell carcinoma (RCC), yet its formation mechanisms remain unclear. Here, we perform integrative single-cell and spatial transcriptomic analyses on 71 tissues and 48 sections from RCC patients with or without TT. The cellular and spatial atlas reveals distinct TT-associated tumor microenvironment remodeling characterized by the enrichment of
FAP
+
fibroblasts. These
FAP
+
fibroblasts are spatially contiguous to aggressive cancer cells and promote their malignant phenotypes in vitro. Their abundance inversely correlates with functional NK cells, suggesting roles in tumor invasion and immune evasion. Furthermore, single-cell multiomics analysis identifies tumor pericytes as a source of
FAP
+
fibroblasts and delineates transcription factor dynamics underlying pericyte-fibroblast transition. Finally, high levels of
FAP
+
fibroblasts are associated with poor prognosis and predict a weaker response to anti-VEGF-based therapy. In conclusion, our study highlights
FAP
+
fibroblasts as drivers of aggressive RCC with TT, suggesting potential therapeutic targets.
Tumour thrombus (TT) complicates renal cell carcinoma (RCC) treatment. Here, authors conduct an integrative single-cell RNA sequencing and spatial transcriptomic analyses on RCC patients with and without TT and identify
FAP
+ fibroblasts as drivers for TT formation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38
/ 38/91
/ Cancer
/ Cancer-Associated Fibroblasts - metabolism
/ Cancer-Associated Fibroblasts - pathology
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - metabolism
/ Carcinoma, Renal Cell - pathology
/ Cells
/ Datasets
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Kidney Neoplasms - metabolism
/ Kidney Neoplasms - pathology
/ Killer Cells, Natural - immunology
/ Male
/ Patients
/ Science
/ Serine Endopeptidases - genetics
/ Serine Endopeptidases - metabolism
/ Tumor Microenvironment - genetics
/ Tumors
