A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling
Autor: | Bernard Thienpont, Valentina Pomella, Hanne Vos, Siel Olbrecht, Marlies Vanden Bempt, Birgit Weynand, Diether Lambrechts, Sara Verbandt, Junbin Qian, Yannick Van Herck, Els Wauters, Ann Smeets, A. Franken, Asier Antoranz, Jieyi Xiong, Ayse Bassez, Sabine Tejpar, Emre Etlioglu, Giuseppe Floris, Francesca Maria Bosisio, Bram Boeckx, Pieter Busschaert, Damya Laoui, Ignace Vergote |
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Přispěvatelé: | Teacher Education, Cellular and Molecular Immunology, Department of Bio-engineering Sciences, Faculty of Sciences and Bioengineering Sciences, Faculty of Arts and Philosophy |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Dendritic Cells/metabolism
medicine.medical_treatment Cellular differentiation Cell Monocytes Tumour biomarkers 0302 clinical medicine Single-cell analysis Neoplasms single-cell analysis RNA-Seq Fibroblasts/metabolism 0303 health sciences education.field_of_study B-Lymphocytes Monocytes/pathology Melanoma B-Lymphocytes/immunology Cell Differentiation Neoplasms/genetics Killer Cells Natural Gene Expression Regulation Neoplastic medicine.anatomical_structure Phenotype Organ Specificity Killer Cells Natural/immunology Tumour immunology TUMOR MICROENVIRONMENT Cancer microenvironment Cell type Stromal cell Macrophages/pathology Tumour heterogeneity Population Stromal Cells/metabolism Biology Endothelial Cells/metabolism Article 03 medical and health sciences Breast cancer Stochastic processes medicine Humans education Molecular Biology 030304 developmental biology Tumor microenvironment Macrophages Endothelial Cells Immunotherapy Cell Biology Dendritic Cells Fibroblasts medicine.disease Cancer cell Cancer research reproducibility of results Stromal Cells 030217 neurology & neurosurgery |
Zdroj: | Cell Research |
Popis: | The stromal compartment of the tumor microenvironment consists of a heterogeneous set of tissue-resident and tumor-infiltrating cells, which are profoundly moulded by cancer cells. An outstanding question is to what extent this heterogeneity is similar between cancers affecting different organs. Here, we profile 233,591 single cells from patients with lung, colorectal, ovary and breast cancer (n = 36) and construct a pan-cancer blueprint of stromal cell heterogeneity using different single-cell RNA and protein-based technologies. We identify 68 stromal cell populations, of which 46 are shared between cancer types and 22 are unique. We also characterise each population phenotypically by highlighting its marker genes, transcription factors, metabolic activities and tissue-specific expression differences. Resident cell types are characterised by substantial tissue specificity, while tumor-infiltrating cell types are largely shared across cancer types. Finally, by applying the blueprint to melanoma tumors treated with checkpoint immunotherapy and identifying a naïve CD4+ T-cell phenotype predictive of response to checkpoint immunotherapy, we illustrate how it can serve as a guide to interpret scRNA-seq data. In conclusion, by providing a comprehensive blueprint through an interactive web server, we generate the first panoramic view on the shared complexity of stromal cells in different cancers. ispartof: CELL RESEARCH vol:30 issue:9 pages:745-762 ispartof: location:England status: published |
Databáze: | OpenAIRE |
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