Cellular architecture of human brain metastases.

Adult Aged Animals Biomarkers, Tumor / metabolism Brain Neoplasms / blood Cell Cycle Cell Line, Tumor Cell Proliferation Female Genetic Variation Humans Immune Evasion Lymphocyte Activation / immunology Lymphocytes, Tumor-Infiltrating / immunology Mice, Inbred BALB C Mice, Nude Middle Aged Models, Biological Myeloid Cells / pathology Principal Component Analysis RNA-Seq Single-Cell Analysis T-Lymphocytes / immunology
CyTOF blood tumor barrier human metastasis metastasis-associated macrophages metastasis-infiltrated T cells metastatic niche metastatic program metastatic tumor cells metastatic tumors single cell

Journal

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

Informations de publication

Date de publication:
17 02 2022
Historique:
received: 02 07 2021
revised: 12 11 2021
accepted: 23 12 2021
pubmed: 23 1 2022
medline: 11 3 2022
entrez: 22 1 2022
Statut: ppublish

Résumé

Brain metastasis (BrM) is the most common form of brain cancer, characterized by neurologic disability and an abysmal prognosis. Unfortunately, our understanding of the biology underlying human BrMs remains rudimentary. Here, we present an integrative analysis of >100,000 malignant and non-malignant cells from 15 human parenchymal BrMs, generated by single-cell transcriptomics, mass cytometry, and complemented with mouse model- and in silico approaches. We interrogated the composition of BrM niches, molecularly defined the blood-tumor interface, and revealed stromal immunosuppressive states enriched with infiltrated T cells and macrophages. Specific single-cell interrogation of metastatic tumor cells provides a framework of 8 functional cell programs that coexist or anticorrelate. Collectively, these programs delineate two functional BrM archetypes, one proliferative and the other inflammatory, that are evidently shaped through tumor-immune interactions. Our resource provides a foundation to understand the molecular basis of BrM in patients with tumor cell-intrinsic and host environmental traits.

Identifiants

DOI: 10.1016/j.cell.2021.12.043 PMID: 35063085 PMC: PMC8857062
pubmed: 35063085
pii: S0092-8674(21)01565-8
doi: 10.1016/j.cell.2021.12.043
pmc: PMC8857062
mid: NIHMS1768870
pii:
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

729-745.e20

Subventions

Organisme : NIAID NIH HHS
ID : R56 AI104789
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI091580
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120724
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199315
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097257
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA057621
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI104789
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA187318
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA190851
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA180039
Pays : United States
Organisme : NIH HHS
ID : DP5 OD023056
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Hugo Gonzalez (H)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA. Electronic address: hugo.gonzalezvelozo@ucsf.edu.

Wenbin Mei (W)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.

Isabella Robles (I)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.

Catharina Hagerling (C)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA; Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, SE 221 85 Lund, Sweden.

Breanna M Allen (BM)

Graduate Program in Biomedical Sciences, University of California, San Francisco, San Francisco, CA, USA; Departments of Otolaryngology-Head and Neck Surgery and Microbiology & Immunology, Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA, USA.

Trine Line Hauge Okholm (TL)

Departments of Otolaryngology-Head and Neck Surgery and Microbiology & Immunology, Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA, USA.

Ankitha Nanjaraj (A)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.

Tamara Verbeek (T)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.

Sandhya Kalavacherla (S)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.

Merel van Gogh (M)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.

Stephen Georgiou (S)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.

Mariza Daras (M)

Department of Neurological Surgery, University of California, San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA.

Joanna J Phillips (JJ)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA; Department of Neurological Surgery, University of California, San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA.

Matthew H Spitzer (MH)

Graduate Program in Biomedical Sciences, University of California, San Francisco, San Francisco, CA, USA; Departments of Otolaryngology-Head and Neck Surgery and Microbiology & Immunology, Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.

Jeroen P Roose (JP)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA. Electronic address: jeroen.roose@ucsf.edu.

Zena Werb (Z)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Cellular architecture of human brain metastases.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Cellular architecture of human brain metastases.
questionsmedicales.fr › Eucaryotes › Animaux › Cellular architecture of human brain metastases.
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Cellular architecture of human brain metastases.
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Cellular architecture of human brain metastases.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › Cellular architecture of human brain metastases.
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cellular architecture of human brain metastases.
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Cellular architecture of human brain metastases.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Cellular architecture of human brain metastases.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cellular architecture of human brain metastases.
questionsmedicales.fr › Phénomènes biologiques › Interactions hôte-microbes › Interactions hôte-pathogène › Échappement immunitaire › Cellular architecture of human brain metastases.
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › Cellular architecture of human brain metastases.
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes TIL › Cellular architecture of human brain metastases.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Cellular architecture of human brain metastases.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris nude › Cellular architecture of human brain metastases.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Cellular architecture of human brain metastases.
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Cellular architecture of human brain metastases.
questionsmedicales.fr › Cellules › Cellules myéloïdes › Cellular architecture of human brain metastases.
questionsmedicales.fr › Techniques d'investigation › Analyse en composantes principales › Cellular architecture of human brain metastases.
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › RNA-Seq › Cellular architecture of human brain metastases.
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › Cellular architecture of human brain metastases.
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Cellular architecture of human brain metastases.