ArticleCancer cell2025
Conserved spatial subtypes and cellular neighborhoods of cancer-associated fibroblasts revealed by single-cell spatial multi-omics.
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Article in Cancer cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers.
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178citing papers in PubMed
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Who cites it
178 citing papers in PubMed.
- IGF2BP2 remodels the lung metastatic immune microenvironment to promote bladder cancer metastasis.Cellular & molecular immunology · 2026Article
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Single-cell epigenomics of colorectal cancer.Experimental & molecular medicine · 2026Review
- Cholangiocarcinoma:Unveiling the cold tumor microenvironment and strategies for immune rejuvenation.Oncogene · 2026Review
- Prefibrotic bone marrow microenvironment is a hallmark of clonal hematopoiesis.Nature immunology · 2026Article
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Integrated Multi-Omics Reveals Cellular States and Microenvironmental Remodeling in Coexisting DCIS and IDC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The dual-enhanced graph learning framework DePass allows paired data integration in single-cell and spatial multiomics.Nature cell biology · 2026Article
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
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- The spatial architecture of tumor immunity: Emerging predictive biomarkers across cancer.Immunologic research · 2026Review
- The FAP × CD3 bispecific antibody OMTX305 induces T cell-mediated antitumor effects in patient-derived ex vivo models of solid tumors.Science advances · 2026Article
- SDC1Gut · 2026Article
- Microenvironment-aware transcriptome reconstruction in spatial transcriptomics.Nature communications · 2026Article
- Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities.Redox biology · 2026Review
- Microarray chip to fabricate 3D PDAC heterospheroids with architectural organization towards tumor invasion and chemoresistance study.Microsystems & nanoengineering · 2026Article
- Cancer-Associated Fibroblasts Promote Glucose Metabolic Reprogramming and Progression of Triple-Negative Breast Cancer via Exosomal circFAD104-Mediated Intercellular Communication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Evolution of FAP-Targeted CAR T-Cell Therapy in Solid Tumors: From Immunotherapy to Immunotheranostic Applications.International journal of molecular sciences · 2026Review
- Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer.Cancer research · 2026Article
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
118 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors.
Yunhe LiuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ansam SinjabDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jimin MinDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Guangchun HanDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Francesca ParadisoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yuanyuan ZhangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ruiping WangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Guangsheng PeiDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yibo DaiDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences (GSBS), Houston, TX 77030, USA.
Yang LiuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Kyung Serk ChoDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Enyu DaiDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Akshay BasiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jared K BurksDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Kimal I RajapaksheSheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yanshuo ChuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jiahui JiangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Daiwei ZhangDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Xinmiao YanDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Paola A GuerreroDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Alejandra SerranoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mingyao LiDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tae Hyun HwangDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Andrew FutrealDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jaffer A AjaniDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Luisa M Solis SotoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Amir A JazaeriDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Humam KadaraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences (GSBS), Houston, TX 77030, USA. Electronic address: hkadara@mdanderson.org.
Anirban MaitraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: amaitra@mdanderson.org.
Linghua WangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences (GSBS), Houston, TX 77030, USA; The James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Institute for Data Science in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: lwang22@mdanderson.org.
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8MZACOPRIDE VS METOCLOPRAMIDE--EFFECT ON LOWER ESOPHAGEAL SPHINCTERM01RR000847 · NCRR · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI KRAMER, CHRISTOPHER M. · 1985 to 2010
$48.1MProject 3: Inhibiting Oxidative Phosphorylation in Pancreatic CancerP50CA221707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT · 2019 to 2023
$11.0MTumor Microenvironment Crosstalk Drives Early Lesions in Pancreatic CancerU54CA274371 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Elana Fertig · 2022 to 2026
$9.5MCenter for Gastric Pre-Cancer Atlas of Multidimensional Evolution in 3D (GAME3D)U01CA294518 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Paul F Mansfield, Linghua Wang · 2024 to 2026
$5.4MPASSCODE (Pancreatic Adenocarcinoma Stromal Reprograming ConSortium COordination, Data Management and Education)U24CA274274 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI J. Jack LEE, ANIRBAN MAITRA · 2022 to 2026
$4.9MTumor cell lineage diversity and composition in gastric cancer progression and therapy resistanceR01CA266280 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Pawel K. Mazur, Linghua Wang · 2022 to 2026
$3.2MSpatial and temporal tumor-immune co-evolution and interactions that model lung adenocarcinoma developmentU01CA264583 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Humam Kadara, Linghua Wang · 2022 to 2026
$2.1MDevelopment of the MasSpec Pen Technology to Guide Surgical Decisions in the Care for Patients with Ovarian CancerR01CA306089 · NCI · BAYLOR COLLEGE OF MEDICINE · PI AMIR A JAZAERI, ANIL K SOOD · 2025 to 2026
$1.4MSingle Cell Spatial Analysis in TissueR50CA243707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BURKS, JARED KYLE · 2020 to 2024
$1.3MEnhanced Machine Learning Tools for Complex Data Evaluation and Integration in Advancing Health OutcomesR01HL173044 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Baiming Zou, Fei Zou · 2025 to 2026
$1.3MNovaSeq6000S10OD024977 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HUFF, VICKI · 2018 to 2018
$995kNCI NIH HHS L30 CA123720NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA221707NCI NIH HHS R01 CA266280NCI NIH HHS R01 CA306089NCI NIH HHS R50 CA243707NCI NIH HHS U01 CA264583NCI NIH HHS U01 CA294518NCI NIH HHS U24 CA274274NCI NIH HHS U54 CA274371NCRR NIH HHS M01 RR000847NHLBI NIH HHS R01 HL173044NIH HHS S10 OD024977
Abstract
Cancer-associated fibroblasts (CAFs) are a multifaceted cell population essential for shaping the tumor microenvironment (TME) and influencing therapy responses. Characterizing the spatial organization and interactions of CAFs within complex tissue environments provides critical insights into tumor biology and immunobiology. In this study, through integrative analyses of over 14 million cells from 10 cancer types across 7 spatial transcriptomics and proteomics platforms, we discover, validate, and characterize four distinct spatial CAF subtypes. These subtypes are conserved across cancer types and independent of spatial omics platforms. Notably, they exhibit distinct spatial organizational patterns, neighboring cell compositions, interaction networks, and transcriptomic profiles. Their abundance and composition vary across tissues, shaping TME characteristics, such as levels, distribution, and state composition of tumor-infiltrating immune cells, tumor immune phenotypes, and patient survival. This study enriches our understanding of CAF spatial heterogeneity in cancer and paves the way for novel approaches to target and modulate CAFs.
Indexed as
Cancer-Associated FibroblastsNeoplasmsProteomicsSingle-Cell AnalysisTumor MicroenvironmentGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMultiomicsTranscriptomecancer-associated fibroblastcell-cell communicationcellular neighborhoodlymphoid aggregatepan-cancerspatial multi-omicsspatial transcriptomicstertiary lymphoid structuretumor associated macrophagetumor microenvironment
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