ArticleCancer research2024
Single-Cell Analysis Identifies NOTCH3-Mediated Interactions between Stromal Cells That Promote Microenvironment Remodeling and Invasion in Lung Adenocarcinoma.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Immunosuppressive roles of pericytes in cancer disease: insights from a systematic review and meta-analysis.Journal of translational medicine · 2026Pooled it
- Pooled it
- Lymph node extracellular matrix skews the immune function of human fibroblastic reticular cells.iScience · 2026Article
- The CRABP2-MDK Signaling Axis Promotes Lung Adenocarcinoma (LUAD) Progression and Highlights Prognostic Biomarkers.Molecular carcinogenesis · 2026Article
- Senescence-directed nanotherapy ameliorates fibrosis and overcomes immune exclusion in cancer.Science (New York, N.Y.) · 2026Article
- Endothelial PERK restricts lymphoid regeneration by reducing DLL4-NOTCH3 signaling at the Pre-B niche.Cell reports · 2026Article
- AGTR1 signaling contributes to tumor immunity and therapy response in non-small cell lung cancer.Molecular therapy. Oncology · 2026Article
- Lung Pericytes: Molecular Mechanisms, Signaling Pathways, and Roles in Pulmonary Diseases.Comprehensive Physiology · 2026Review
- Deciphering lung cancer at high resolution: a narrative review of applications of single-cell and spatial transcriptomics sequencing.Translational lung cancer research · 2026Review
- Characterization of natural killer (NK) cells in lung adenocarcinoma and construction of an NK risk signature based on single-cell and macromolecular RNA-seg data.Discover oncology · 2026Article
- A convergent uPAR-positive tumor ecosystem creates broad vulnerability to CAR T cell therapy.Cell · 2026Article
- In vitro models of cancer-associated fibroblast heterogeneity uncover subtype-specific effects of CRISPR perturbations.Molecular oncology · 2026Article
- Functional analysis of the human miRNome in non-small cell lung cancer unveils a novel miR-92b-3p/NOTCH3 axis that drives tumor progression.Cell death & disease · 2026Article
- Article
- FOSL1 promotes homologous recombination repair and camptothecin resistance via TCOF1-mediated ribosome biogenesis in non-small cell lung cancer.Translational oncology · 2026Article
- LINC01116, a hypoxia-lncRNA marker of pathological lymphangiogenesis and poor prognosis in lung adenocarcinoma.Molecular oncology · 2026Article
- Identification of a Prognostic Gene Signature for Chemoresistance Prediction in Lung Adenocarcinoma by Screening Mitochondrial Metabolism Gene Sets.International journal of molecular sciences · 2026Article
- Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma.Nature communications · 2026Article
- Reconstructing multi-scale tissue spatial architecture from single-cell RNA-seq with REMAP.bioRxiv : the preprint server for biology · 2026Article
- NOTCH3 attenuates cytotoxicity via RBPJ-dependent PVR upregulation to influence immunotherapy outcomes in colorectal cancer.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
29 authors at 4 institutions in 2 countries.
Funding
Abstract
Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant proportion of patients do not respond. Recent transcriptomic studies to understand determinants of immunotherapy response have pinpointed stromal-mediated resistance mechanisms. To gain a better understanding of stromal biology at the cellular and molecular level in LUAD, we performed single-cell RNA sequencing of 256,379 cells, including 13,857 mesenchymal cells, from 9 treatment-naïve patients. Among the mesenchymal cell subsets, FAP+PDPN+ cancer-associated fibroblasts (CAF) and ACTA2+MCAM+ pericytes were enriched in tumors and differentiated from lung-resident fibroblasts. Imaging mass cytometry revealed that both subsets were topographically adjacent to the perivascular niche and had close spatial interactions with endothelial cells (EC). Modeling of ligand and receptor interactomes between mesenchymal and ECs identified that NOTCH signaling drives these cell-to-cell interactions in tumors, with pericytes and CAFs as the signal receivers and arterial and PLVAPhigh immature neovascular ECs as the signal senders. Either pharmacologically blocking NOTCH signaling or genetically depleting NOTCH3 levels in mesenchymal cells significantly reduced collagen production and suppressed cell invasion. Bulk RNA sequencing data demonstrated that NOTCH3 expression correlated with poor survival in stroma-rich patients and that a T cell-inflamed gene signature only predicted survival in patients with low NOTCH3. Collectively, this study provides valuable insights into the role of NOTCH3 in regulating tumor stroma biology, warranting further studies to elucidate the clinical implications of targeting NOTCH3 signaling. SIGNIFICANCE: NOTCH3 signaling activates tumor-associated mesenchymal cells, increases collagen production, and augments cell invasion in lung adenocarcinoma, suggesting its critical role in remodeling tumor stroma.
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Registered trials
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 Socratic graph.