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Cellular architecture of human brain metastases
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- Gonzalez, Hugo (author)
- University of California, San Francisco
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- Mei, Wenbin (author)
- University of California, San Francisco
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- Robles, Isabella (author)
- University of California, San Francisco
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- (creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
- In: Cell. - : Elsevier BV. - 0092-8674. ; 185:4, s. 20-745
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- blood tumor barrier
- CyTOF
- human metastasis
- metastasis-associated macrophages
- metastasis-infiltrated T cells
- metastatic niche
- metastatic program
- metastatic tumor cells
- metastatic tumors
- single cell
Publication and Content Type
- art (subject category)
- ref (subject category)
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- MEDICAL AND HEALTH SCIENCES
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- Cell
- By the university
- Lund University
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