Dissecting the treatment-naive ecosystem of human melanoma brain metastasis.

Autor:	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 Jr; 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., Bruce JN; Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA., Bi WL; Department 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., Agrawal P; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA., Schapiro D; Heidelberg 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., Hernando E; Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA., Macosko EZ; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA., Chen F; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA., Schwartz GK; Department of Medicine, Division of Hematology/Oncology, and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA., Izar B; 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; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: bi2175@cumc.columbia.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2022 Jul 07; Vol. 185 (14), pp. 2591-2608.e30.
DOI:	10.1016/j.cell.2022.06.007
Abstrakt:	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. Competing Interests: Declaration of interests B.I. has received honoraria from consulting with Merck, Janssen Pharmaceuticals, Astra Zeneca, and Volastra Therapeutics. M.A.D. has been a consultant to Roche/Genentech, Array, Pfizer (New York, NY, United States of America), Novartis, BMS, GSK, Sanofi-Aventis (Bridgewater, NJ, United States of America), Vaccinex, Apexigen, EISAI, and ABM Therapeutics and he has been the PI of research grants to MD Anderson by Roche/Genentech (South San Francisco, CA, United States of America), GSK, Sanofi-Aventis, Merck, Myriad, and Oncothyreon. A.R. has received honoraria from consulting with CStone, Merck, and Vedanta, is or has been a member of the scientific advisory board and holds stock in Advaxis, Appia, Apricity, Arcus, Compugen, CytomX, Highlight, ImaginAb, ImmPact, ImmuneSensor, Inspirna, Isoplexis, Kite-Gilead, Lutris, MapKure, Merus, PACT, Pluto, RAPT, Synthekine, and Tango, has received research funding from Agilent (Santa Clara, CA, United States of America) and from Bristol-Myers Squibb through Stand Up to Cancer (SU2C), and patent royalties from Arsenal Bio. T.E. has acted as a consultant for Almiral Hermal, Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, and Sanofi. E.Z.M. is a consultant for Curio Bioscience. The other authors do not declare competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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