Cellular architecture of human brain metastases
| Autor: | Hugo Gonzalez, Wenbin Mei, Isabella Robles, Catharina Hagerling, Breanna M. Allen, Trine Line Hauge Okholm, Ankitha Nanjaraj, Tamara Verbeek, Sandhya Kalavacherla, Merel van Gogh, Stephen Georgiou, Mariza Daras, Joanna J. Phillips, Matthew H. Spitzer, Jeroen P. Roose, Zena Werb |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Mice Inbred BALB C Principal Component Analysis Brain Neoplasms T-Lymphocytes Cell Cycle Genetic Variation Mice Nude Middle Aged Lymphocyte Activation Models Biological General Biochemistry Genetics and Molecular Biology Lymphocytes Tumor-Infiltrating Cell Line Tumor Biomarkers Tumor Animals Humans Female Myeloid Cells RNA-Seq Single-Cell Analysis Aged Cell Proliferation Immune Evasion |
| Zdroj: | Cell. 185(4) |
| ISSN: | 1097-4172 |
| Popis: | 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 of100,000 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|