ArticleCell2022
Dissecting the treatment-naive ecosystem of human melanoma brain metastasis.
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Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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132citing papers in PubMed
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Who cites it
132 citing papers in PubMed.
- Spatially-resolved single-cell imaging of melanoma brain metastases identifies localized immune patterns predictive of immune checkpoint blockade response.Neuro-oncology · 2026Article
- Tumor microenvironment and signaling pathways in melanoma brain metastasis.Annals of translational medicine · 2026Review
- Patient-derived resources for decoding and targeting brain metastases ecosystems.EMBO molecular medicine · 2026Review
- Article
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- Article
- A Targetable Developmental Program Coregulates Angiogenesis and Immune Evasion in Melanoma.Cancer discovery · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Targeting noncanonical nuclear factor kappa B signalling in CYLD cutaneous syndrome by selective inhibition of IκB kinase alpha.The British journal of dermatology · 2026Article
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- Brain metastases converge on shared geometric architecture and transcriptomic landscape yet remain distinct from gliomas.iScience · 2026Article
- Single-cell and spatial profiling in cancer biology and clinical oncology.Nature cancer · 2026Review
- Single-cell advances in the investigation of the pathogenesis and treatment of brain metastasis.Neuro-oncology advances · 2026Review
- Benchmarking cell-type-specific spatially variable gene detection methods.Briefings in bioinformatics · 2026Article
- Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.International journal of molecular sciences · 2026Review
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Spatial architecture of development and disease.Nature reviews. Genetics · 2026Review
- A proteogenomic atlas of 1032 brain metastases identifies molecular subtypes, immune landscapes, and therapeutic vulnerabilities.Nature communications · 2026Article
72 more citing papers are in PubMed but not listed here.
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Authors and funding
59 authors.
Jana BiermannDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Program for Mathematical Genomics, Columbia University, New York, NY 10032, USA.
Johannes C MelmsDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Amit Dipak AminDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Yiping WangDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Program for Mathematical Genomics, Columbia University, New York, NY 10032, USA.
Lindsay A CaprioDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alcida KarzDepartment of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Somnath TagoreDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Irving BarreraBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Miguel A Ibarra-ArellanoHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.
Massimo AndreattaDepartment of Oncology UNIL CHUV, Lausanne Branch, Ludwig Institute for Cancer Research Lausanne, CHUV and University of Lausanne, Lausanne, 1066 Épalinges, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Benjamin T FullertonDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Kristjan H GretarssonDepartment of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Varun SahuDepartment of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Vaibhav S MangipudyDepartment of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Trang T T NguyenDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Ajay NairDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Meri RogavaDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Patricia HoDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Peter D KochColumbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Matei BanuDepartment of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.
Nelson HumalaDepartment of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.
Aayushi MahajanDepartment of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.
Zachary H WalshColumbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Shivem B ShahColumbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Daniel H VaccaroColumbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Blake CaldwellColumbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Michael MuColumbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Florian WünnemannHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.
Margot ChazotteHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.
Simon BerheDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Adrienne M LuomaDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Center, Boston, MA 02215, USA.
Joseph DriverDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Matthew InghamDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Shaheer A KhanDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Suthee RapisuwonDivision of Hematology/Oncology, Medstar Washington Cancer Institute, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Craig L SlingluffDepartment of Surgery, University of Virginia, Charlottesville, VA, USA.
Thomas EigentlerDepartment of Dermatology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany; Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, 10117, Berlin, Germany.
Martin RöckenDepartment of Dermatology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
Richard CarvajalDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Michael B AtkinsGeorgetown-Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Michael A DaviesDepartment of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Albert AgustinusHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pharmacology, Weill Cornell Graduate School, New York, NY 10065, USA.
Samuel F BakhoumDepartment of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Elham AziziDepartment of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
Markus SiegelinDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Chao LuDepartment of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Santiago J CarmonaDepartment of Oncology UNIL CHUV, Lausanne Branch, Ludwig Institute for Cancer Research Lausanne, CHUV and University of Lausanne, Lausanne, 1066 Épalinges, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Hanina HibshooshDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Antoni RibasDepartment of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA 90024, USA.
Peter CanollDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Jeffrey N BruceDepartment of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.
Wenya Linda BiDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Praveen AgrawalDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Denis SchapiroHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany; Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Eva HernandoDepartment of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Evan Z MacoskoBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.
Fei ChenBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Gary K SchwartzDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Benjamin IzarDepartment of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Program for Mathematical Genomics, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: bi2175@cumc.columbia.edu.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ANIRBAN MAITRA · 1985 to 2026
$83.1MTissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI Louis M Weiner · 1990 to 2026
$71.5MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007367 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI REINER, STEVEN L · 1985 to 2021
$25.1MResearch Project 2 - Targeting Melanoma Tumor Survival and Apoptotic MachineryU54CA224070 · NCI · WISTAR INSTITUTE · PI Meenhard F Herlyn · 2017 to 2026
$13.9MProject 4P50CA225450 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KIRCHHOFF, TOMAS · 2019 to 2025
$12.5MProject 3: The Evolving Role of Regional Lymph Nodes in Melanoma ProgressionU54CA263001 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Eva Hernando, Iman Osman · 2022 to 2026
$11.6MSystems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8MNext Generation Cancer Immunotherapies to Defeat MelanomaR35CA197633 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTONI RIBAS · 2015 to 2026
$10.4MThe University of Texas MD Anderson Cancer Center SPORE in MelanomaP50CA221703 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAVIES, MICHAEL · 2019 to 2023
$10.3MNCI NIH HHS K08 CA222663NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA013696NCI NIH HHS P30 CA016087NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA051008NCI NIH HHS P50 CA221703NCI NIH HHS P50 CA225450NCI NIH HHS R01 CA256188NCI NIH HHS R21 CA263381NCI NIH HHS R35 CA197633NCI NIH HHS R37 CA258829NCI NIH HHS U54 CA224070NCI NIH HHS U54 CA225088NCI NIH HHS U54 CA263001NIAID NIH HHS T32 AI148099NIGMS NIH HHS T32 GM007367NIGMS NIH HHS T32 GM136573NIGMS NIH HHS T32 GM145440NIH HHS DP5 OD026395
Abstract
Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX
Indexed as
Brain NeoplasmsMelanomaCD8-Positive T-LymphocytesEcosystemHumansRNA-Seqbrain metastasischromosomal instabilitymelanomaneuronal-like cell statesingle-cell genomicsspatial transcriptomicstumor-microenvironment
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