ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Spatial Transcriptomics and snRNA-seq Expose CAF Niches Orchestrating Dual Stromal-Immune Barriers in Hepatocellular Carcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Epstein-Barr virus-driven immunosuppression in nasopharyngeal carcinoma: a comprehensive review of viral mechanisms, spatial tumor ecosystems, and precision therapeutics.Frontiers in immunology · 2026Pooled it
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- The Role of Direct-Acting Antivirals (DAAs) in Hepatitis C Virus-Associated Lymphoproliferative Disorders.Cancers · 2026Review
- Integrated miRNA Sequencing and Network Analysis Reveal a Molecular Continuum Between Peritumoral and Tumor Tissue in Prostate Cancer.International journal of molecular sciences · 2026Article
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Single-cell insights into hepatic fibroblasts and stellate cells: heterogeneity in matrix remodelling in development, health, and disease.Npj gut and liver · 2026Review
- Integrative multi-omics reveals the POSTNFrontiers in immunology · 2026Article
- Immunosuppressive cells as barriers to cancer therapy: mechanisms and emerging solutions.Frontiers in immunology · 2026Review
- Spatial compartmentalization of melanoma cell states reveals CAF-associated tumor cells with enhanced proliferative capacity.PloS one · 2026Article
- Molecular mechanisms and clinical significance of the glioma metabolic-immune axis: a comprehensive review.Frontiers in immunology · 2026Review
- IntegratingFrontiers in immunology · 2026Review
- Formation and remodeling of immunological niches in solid tumors: organ-specific architectures, inflammatory parallels, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Integrative multi-omics identifies PANX2 as a ferroptosis suppressor and potential therapeutic target in clear cell renal cell carcinoma.Frontiers in immunology · 2026Article
- The invasive front in hepatocellular carcinoma: toward a tumor-CAF-macrophage metabolic interface.Frontiers in immunology · 2026Article
- Spatial Transcriptomics and snRNA-seq Expose CAF Niches Orchestrating Dual Stromal-Immune Barriers in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) exhibits profound spatial heterogeneity driving therapeutic resistance, while the role of cancer-associated fibroblasts (CAFs) in orchestrating immunosuppressive niches remains incompletely defined. This study integrates single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (stRNA-seq) to map the cellular and molecular landscape of HCC. snRNA-seq identifies key cell populations-including fibroblasts, T_NK cells, and endothelial cells-using canonical marker genes. Spatial transcriptomics maps gene expression across tumor regions (core, invasive front, stroma) via the robust cell type decomposition (RCTD) algorithm. Immunofluorescence validates collagen deposition and POSTN spatial distribution, confirming T-cell exclusion patterns. The analysis identifies hypoxic metabolic myofibroblasts (hmmyCAFs) as central regulators of the tumor microenvironment. hmmyCAFs enrich at the invasive front, forming collagen-rich barriers that physically exclude CD8⁺ T cells. Simultaneously, they secrete POSTN to suppress immune checkpoint signaling and drive hypoxia-mediated glycolytic reprogramming of T-cell metabolism. Clinically, hmmyCAF activity and POSTN expression correlate with reduced progression-free survival and immunotherapy resistance. This multimodal study defines hmmyCAFs as triple architects of physical immunosuppression, molecular regulation, and metabolic remodeling. By linking collagen remodeling, POSTN-mediated checkpoint inhibition, and hypoxia-driven metabolic reprogramming to clinical outcomes, hmmyCAFs and POSTN may serve as potential indicators for evaluating the efficacy of immunotherapy in HCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.