ArticleCancer cell2022
Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.
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Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
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154citing papers in PubMed
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Who cites it
154 citing papers in PubMed, 196 citations in OpenAlex.
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- Local, but not circulating, complement C3 shapes immune checkpoint blockade efficacy by controlling myeloid cell infiltration.Nature communications · 2026Article
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
- Multi-omics analysis identifies a major histocompatibility complex class II-associated antigen-presenting cancer-associated fibroblast-like state linked to the nuclear factor erythroid 2-related factor 2-karyopherin subunit beta 1 axis in nonsmall cell lung cancer.Journal of cell communication and signaling · 2026Article
- Fibroblasts as regulators of lung immunity, repair and fibrosis.Nature reviews. Immunology · 2026Review
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Targeting LRRC15 in Cancer-Associated Fibroblasts Modifies the Extracellular Matrix and Enhances Tumor Immune Responses to Suppress Lung Cancer Progression.Cancer research · 2026Article
- E-cadherin inactivation shapes tumor microenvironment specificities in invasive lobular breast cancer.Nature communications · 2026Article
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Cancer-associated fibroblasts and immune escape-related genes serve as biological markers for the prognosis of colorectal cancer.Hereditas · 2026Article
- Spatial and functional polarization of cancer-associated fibroblasts with CXCR4-mediated immune modulation in hepatocellular carcinoma.Hepatology communications · 2026Article
- An Insulin-Exosome-TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Heterogeneity and plasticity of cancer-associated fibroblasts.Nature cancer · 2026Review
94 more citing papers are in PubMed but not listed here.
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Authors and funding
36 authors at 4 institutions in 1 country.
Deshka S FosterHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
Michael JanuszykHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Daniel DelittoHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
Kathryn E YostCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Michelle GriffinHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jason GuoHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nicholas GuardinoHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Andrea E DelittoHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
Malini ChintaHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Austin R BurchamHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alan T NguyenHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Khristian E Bauer-RoweHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ashley L TitanHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
Ankit SalhotraHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
R Ellen JonesHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Oscar da SilvaHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hunter G LindsayHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Charlotte E BerryHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kellen ChenHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dominic HennHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Shamik MascharakHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Heather E TalbottHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alexia KimHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Fatemeh NosratiHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dharshan SivarajHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
R Chase RansomHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michael MatthewsHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Anum KhanCell Sciences Imaging Facility, Stanford University, Stanford, CA 94305, USA.
Dhananjay WaghStanford Genomics Facility, Stanford University, Stanford, CA 94305, USA.
John CollerStanford Genomics Facility, Stanford University, Stanford, CA 94305, USA.
Geoffrey C GurtnerHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
Derrick C WanHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
Irene L WapnirDepartment of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. Electronic address: howchang@stanford.edu.
Jeffrey A NortonHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA. Electronic address: janorton@stanford.edu.
Michael T LongakerHagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: longaker@stanford.edu.
Stanford University · USStanford Medicine · USCalifornia Institute for Regenerative Medicine · USHoward Hughes Medical Institute · US
Funding
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4MCenter for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8MLncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4MThe University of Arizona Wound Care Center Clinical Research UnitU01DK119094 · NIDDK · UNIVERSITY OF ARIZONA · PI GEOFFREY C GURTNER, Wei Zhou · 2018 to 2026
$5.1MIrradiated head and neck cancer soft tissue reconstruction by fat transfer.R01DE027346 · NIDCR · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WAN, DERRICK · 2018 to 2022
$1.9MMechanoresponsive Engrailed-1-negative fibroblasts activate Engrailed-1 to promote fibrosis in wound healingR01GM136659 · NIGMS · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T · 2020 to 2023
$1.3MFibroblast lineage mechanisms of scarless skin healingR01GM116892 · NIGMS · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, LORENZ, HERMANN PETER · 2017 to 2020
$1.2MUltra high throughput sequencer for sustaining and enhancing multi-scale genomic studiesS10OD025212 · OD · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2018 to 2018
$600kHigh Throughput DNA Sequencer UpgradeS10OD018220 · OD · STANFORD UNIVERSITY · PI COLLER, JOHN · 2014 to 2014
$596kNikon A1Rsi resonant spectral confocal microscopeS10OD010580 · OD · STANFORD UNIVERSITY · PI FULLER, MARGARET T · 2013 to 2013
$377kCANCER ASSOCIATED FIBROBLAST CLONALITY, CHROMATIN ACCESSIBILITY AND THERAPEUTIC TARGETING IN PANCREATIC DUCTAL ADENOCARCINOMA STROMAF32CA239312 · NCI · STANFORD UNIVERSITY · PI FOSTER, DESHKA STONOROV · 2020 to 2020
$53kNCI NIH HHS F32 CA239312NCI NIH HHS P30 CA124435NCI NIH HHS R35 CA209919NHGRI NIH HHS RM1 HG007735NIDCR NIH HHS R01 DE027346NIDDK NIH HHS U01 DK119094NIGMS NIH HHS R01 GM116892NIGMS NIH HHS R01 GM136659NIH HHS S10 OD010580NIH HHS S10 OD018220NIH HHS S10 OD025212
Abstract
Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cell chromatin accessibility and transcriptome analysis, we provided an integrated analysis of CAF subpopulations over a complex spatial transcriptomic and proteomic landscape to identify three superclusters: steady state-like (SSL), mechanoresponsive (MR), and immunomodulatory (IM) CAFs. These superclusters are recapitulated across multiple tissue types and species. Selective disruption of underlying mechanical force or immune checkpoint inhibition therapy results in shifts in CAF subpopulation distributions and affected tumor growth. As such, the balance among CAF superclusters may have considerable translational implications. Collectively, this research expands our understanding of CAF biology, identifying regulatory pathways in CAF differentiation and elucidating therapeutic targets in a species- and tumor-agnostic manner.
Indexed as
Cancer-Associated FibroblastsNeoplasmsHumansPhenotypeProteomicsTumor MicroenvironmentATAC-seqcancerCODEXfibroblastsmechanotransductionmulti-omicsRNA-seqsingle cellspatial transcriptomics
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