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

Brain Neoplasms / drug therapy CD8-Positive T-Lymphocytes / pathology Ecosystem Humans Melanoma RNA-Seq
brain metastasis chromosomal instability melanoma neuronal-like cell state single-cell genomics spatial transcriptomics tumor-microenvironment

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
07 07 2022
Historique:
received: 01 10 2021
revised: 08 04 2022
accepted: 06 06 2022
entrez: 8 7 2022
pubmed: 9 7 2022
medline: 14 7 2022
Statut: ppublish

Résumé

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

Identifiants

DOI: 10.1016/j.cell.2022.06.007 PMID: 35803246 PMC: PMC9677434
pubmed: 35803246
pii: S0092-8674(22)00712-7
doi: 10.1016/j.cell.2022.06.007
pmc: PMC9677434
mid: NIHMS1819979
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2591-2608.e30

Subventions

Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136573
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007367
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA222663
Pays : United States
Organisme : NIH HHS
ID : DP5 OD026395
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA225450
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197633
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA051008
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA263001
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM145440
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA256188
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224070
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI148099
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA258829
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA225088
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA263381
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221703
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

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Auteurs

Jana 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.

Johannes C 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.

Amit Dipak 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.

Yiping 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.

Lindsay A 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.

Alcida Karz (A)

Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.

Somnath Tagore (S)

Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.

Irving Barrera (I)

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Miguel A Ibarra-Arellano (MA)

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.

Massimo 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.

Benjamin T 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.

Kristjan H Gretarsson (KH)

Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.

Varun Sahu (V)

Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.

Vaibhav S Mangipudy (VS)

Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.

Trang T T Nguyen (TTT)

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.

Ajay 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.

Meri 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.

Patricia 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.

Peter D Koch (PD)

Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Matei Banu (M)

Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.

Nelson Humala (N)

Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.

Aayushi Mahajan (A)

Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.

Zachary H Walsh (ZH)

Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Shivem B Shah (SB)

Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Daniel H Vaccaro (DH)

Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Blake Caldwell (B)

Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Michael Mu (M)

Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Florian Wünnemann (F)

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.

Margot Chazotte (M)

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.

Simon 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.

Adrienne M Luoma (AM)

Department of Cancer Immunology and Virology, Dana-Farber Cancer Center, Boston, MA 02215, USA.

Joseph Driver (J)

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Matthew 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.

Shaheer A 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.

Suthee Rapisuwon (S)

Division of Hematology/Oncology, Medstar Washington Cancer Institute, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.

Craig L Slingluff (CL)

Department of Surgery, University of Virginia, Charlottesville, VA, USA.

Thomas 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.

Martin Röcken (M)

Department of Dermatology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.

Richard 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.

Michael B Atkins (MB)

Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.

Michael A Davies (MA)

Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.

Albert 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.

Samuel F 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.

Elham 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.

Markus Siegelin (M)

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.

Chao Lu (C)

Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.

Santiago J 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.

Hanina Hibshoosh (H)

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.

Antoni Ribas (A)

Department of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA 90024, USA.

Peter Canoll (P)

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.

Jeffrey N Bruce (JN)

Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USA.

Wenya Linda 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.

Praveen Agrawal (P)

Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.

Denis 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.

Eva Hernando (E)

Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.

Evan Z Macosko (EZ)

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.

Fei 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.

Gary K 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.

Benjamin 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.

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Classifications MeSH

questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Dissecting the treatment-naive ecosystem of...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Dissecting the treatment-naive ecosystem of...
questionsmedicales.fr › Environnement et santé publique › Environnement › Écosystème › Dissecting the treatment-naive ecosystem of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Dissecting the treatment-naive ecosystem of...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Dissecting the treatment-naive ecosystem of...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › RNA-Seq › Dissecting the treatment-naive ecosystem of...