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Dissecting the treatment-naive ecosystem of human melanoma brain metastasis.
Biermann, Jana; Melms, Johannes C; Amin, Amit Dipak; Wang, Yiping; Caprio, Lindsay A; Karz, Alcida; Tagore, Somnath; Barrera, Irving; Ibarra-Arellano, Miguel A; Andreatta, Massimo; Fullerton, Benjamin T; Gretarsson, Kristjan H; Sahu, Varun; Mangipudy, Vaibhav S; Nguyen, Trang T T; Nair, Ajay; Rogava, Meri; Ho, Patricia; Koch, Peter D; Banu, Matei; Humala, Nelson; Mahajan, Aayushi; Walsh, Zachary H; Shah, Shivem B; Vaccaro, Daniel H; Caldwell, Blake; Mu, Michael; Wünnemann, Florian; Chazotte, Margot; Berhe, Simon; Luoma, Adrienne M; Driver, Joseph; Ingham, Matthew; Khan, Shaheer A; Rapisuwon, Suthee; Slingluff, Craig L; Eigentler, Thomas; Röcken, Martin; Carvajal, Richard; Atkins, Michael B; Davies, Michael A; Agustinus, Albert; Bakhoum, Samuel F; Azizi, Elham; Siegelin, Markus; Lu, Chao; Carmona, Santiago J; Hibshoosh, Hanina; Ribas, Antoni; Canoll, Peter.
Afiliação
  • Biermann J; Department 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.
  • Melms JC; Department 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.
  • Amin AD; Department 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.
  • Wang Y; Department 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.
  • Caprio LA; Department 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.
  • Karz A; Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Tagore S; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Barrera I; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Ibarra-Arellano MA; Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.
  • Andreatta M; Department 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.
  • Fullerton BT; Department of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Gretarsson KH; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Sahu V; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Mangipudy VS; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Nguyen TTT; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
  • Nair A; Department of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Rogava M; Department 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.
  • Ho P; Department 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.
  • Koch PD; Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Banu M; Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Humala N; Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Mahajan A; Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Walsh ZH; Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Shah SB; Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Vaccaro DH; Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Caldwell B; Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Mu M; Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
  • Wünnemann F; Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.
  • Chazotte M; Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.
  • Berhe S; Department of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Luoma AM; Department of Cancer Immunology and Virology, Dana-Farber Cancer Center, Boston, MA 02215, USA.
  • Driver J; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Ingham M; Department of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Khan SA; Department of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Rapisuwon S; Division of Hematology/Oncology, Medstar Washington Cancer Institute, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
  • Slingluff CL; Department of Surgery, University of Virginia, Charlottesville, VA, USA.
  • Eigentler T; Department 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.
  • Röcken M; Department of Dermatology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
  • Carvajal R; Department of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Atkins MB; Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
  • Davies MA; Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Agustinus A; Human 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.
  • Bakhoum SF; Department 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.
  • Azizi E; Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
  • Siegelin M; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
  • Lu C; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
  • Carmona SJ; Department 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.
  • Hibshoosh H; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
  • Ribas A; Department of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA 90024, USA.
  • Canoll P; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Cell ; 185(14): 2591-2608.e30, 2022 07 07.
Article em En | MEDLINE | ID: mdl-35803246
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+CD8+ T cells with distinct expression of immune checkpoints. This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Melanoma Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Melanoma Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos