ArticleNature communications2023
The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed.
- IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells.Oncoimmunology · 2026Review
- scMustree: a multi-scale functional hierarchy for single-cell transcriptomic analysis.Bioinformatics (Oxford, England) · 2026Article
- Immune Circuit Rewiring by HDAC Inhibition Enables Response to Dual Checkpoint Blockade in Metastatic Breast Cancer.Cancer research · 2026Article
- APOEScience advances · 2026Article
- Reprogramming the Immunosuppressive Microenvironment in Triple-Negative Breast Cancer via FAP-Targeted Nanoprobes for Multimodal Imaging and Photothermal Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- RHOT1/2-driven mitochondrial membrane vesicles confer tumor-homing selectivity and enable in situ cancer vaccination.Nature communications · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.Biomarker research · 2026Review
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
- Head-to-Head Comparison of Monomeric, Homodimeric, and Heterodimeric Fibroblast Activation Protein-Targeting Radioligands Based on Small Molecule Inhibitor and Cyclic Peptide.ACS pharmacology & translational science · 2026Article
- Vaginal Microbiota and Ovarian Cancer: A New Frontier in Immunomodulation and Diagnosis.Immunology · 2026Review
- Modulation of the immunogenic landscape in colorectal cancer by mitochondrial methylation-controlled J protein.Molecular biomedicine · 2026Article
- Beyond the chaos: How architecture structures tumour biology.The FEBS journal · 2026Review
- Single-cell phenotype-associated subpopulation identification via transfer foundation model and statistical ensemble learning.BMC biology · 2026Article
- Heterogeneity and plasticity of cancer-associated fibroblasts.Nature cancer · 2026Review
- Spatial omics study reveals molecular-cellular dynamics of tumor ecosystem in esophageal squamous-cell carcinoma initiation and progression.Cell reports. Medicine · 2026Article
- Reactive Stroma as a Transversal Prognostic Biomarker for Metastasis in Breast Cancer: Integration of Digital Histopathology and Transcriptomic Profiling.International journal of molecular sciences · 2026Article
- A Pan-Cancer Ex Vivo Drug Screen Atlas for Functional Precision Oncology.bioRxiv : the preprint server for biology · 2026Article
- TiRank prioritizes phenotypic niches in tumor microenvironment for clinical biomarker discovery.Genome medicine · 2026Article
- High-dose irradiation promotes macrophage-mediated engulfment of triple-negative breast cancer through M1 polarization via the IKZF1-CCL5 axis.Cell communication and signaling : CCS · 2026Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
The tumor microenvironment (TME) is comprised of non-malignant cells that interact with each other and with cancer cells, critically impacting cancer biology. The TME is complex, and understanding it requires simplifying approaches. Here we provide an experimental-mathematical approach to decompose the TME into small circuits of interacting cell types. We find, using female breast cancer single-cell-RNA-sequencing data, a hierarchical network of interactions, with cancer-associated fibroblasts (CAFs) at the top secreting factors primarily to tumor-associated macrophages (TAMs). This network is composed of repeating circuit motifs. We isolate the strongest two-cell circuit motif by culturing fibroblasts and macrophages in-vitro, and analyze their dynamics and transcriptomes. This isolated circuit recapitulates the hierarchy of in-vivo interactions, and enables testing the effect of ligand-receptor interactions on cell dynamics and function, as we demonstrate by identifying a mediator of CAF-TAM interactions - RARRES2, and its receptor CMKLR1. Thus, the complexity of the TME may be simplified by identifying small circuits, facilitating the development of strategies to modulate the TME.
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