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Cellular architecture of human brain metastases

Gonzalez, Hugo ; Mei, Wenbin ; Robles, Isabella ; Hagerling, Catharina LU ; Allen, Breanna M. ; Hauge Okholm, Trine Line ; Nanjaraj, Ankitha ; Verbeek, Tamara ; Kalavacherla, Sandhya and van Gogh, Merel , et al. (2022) In Cell 185(4). p.20-745
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
blood tumor barrier, CyTOF, human metastasis, metastasis-associated macrophages, metastasis-infiltrated T cells, metastatic niche, metastatic program, metastatic tumor cells, metastatic tumors, single cell
in
Cell
volume
185
issue
4
pages
20 - 745
publisher
Cell Press
external identifiers
  • scopus:85124540472
  • pmid:35063085
ISSN
0092-8674
DOI
10.1016/j.cell.2021.12.043
language
English
LU publication?
yes
id
e7881641-7f1f-4172-8405-1b7a7d2f59d1
date added to LUP
2022-04-12 15:20:32
date last changed
2024-04-07 16:36:51
@article{e7881641-7f1f-4172-8405-1b7a7d2f59d1,
  abstract     = {{<p>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 &gt;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.</p>}},
  author       = {{Gonzalez, Hugo and Mei, Wenbin and Robles, Isabella and Hagerling, Catharina and Allen, Breanna M. and Hauge Okholm, Trine Line and Nanjaraj, Ankitha and Verbeek, Tamara and Kalavacherla, Sandhya and van Gogh, Merel and Georgiou, Stephen and Daras, Mariza and Phillips, Joanna J. and Spitzer, Matthew H. and Roose, Jeroen P. and Werb, Zena}},
  issn         = {{0092-8674}},
  keywords     = {{blood tumor barrier; CyTOF; human metastasis; metastasis-associated macrophages; metastasis-infiltrated T cells; metastatic niche; metastatic program; metastatic tumor cells; metastatic tumors; single cell}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{20--745}},
  publisher    = {{Cell Press}},
  series       = {{Cell}},
  title        = {{Cellular architecture of human brain metastases}},
  url          = {{http://dx.doi.org/10.1016/j.cell.2021.12.043}},
  doi          = {{10.1016/j.cell.2021.12.043}},
  volume       = {{185}},
  year         = {{2022}},
}