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Cellular architecture of human brain metastases.
Gonzalez, Hugo; Mei, Wenbin; Robles, Isabella; Hagerling, Catharina; Allen, Breanna M; Hauge Okholm, Trine Line; Nanjaraj, Ankitha; Verbeek, Tamara; Kalavacherla, Sandhya; van Gogh, Merel; Georgiou, Stephen; Daras, Mariza; Phillips, Joanna J; Spitzer, Matthew H; Roose, Jeroen P; Werb, Zena.
Afiliação
  • Gonzalez H; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA. Electronic address: hugo.gonzalezvelozo@ucsf.edu.
  • Mei W; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
  • Robles I; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
  • 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.
  • 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,
  • 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.
  • Nanjaraj A; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
  • Verbeek T; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
  • Kalavacherla S; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
  • van Gogh M; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
  • Georgiou S; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
  • Daras M; Department of Neurological Surgery, University of California, San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA.
  • 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.
  • 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,
  • Roose JP; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA. Electronic address: jeroen.roose@ucsf.edu.
  • 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.
Cell ; 185(4): 729-745.e20, 2022 02 17.
Article em En | MEDLINE | ID: mdl-35063085
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas Limite: Adult / Aged / Animals / Female / Humans / Middle aged Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas Limite: Adult / Aged / Animals / Female / Humans / Middle aged Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article