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
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