Volume 30, No 9, Sep 2020

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 30 Issue 9, September 2020: 745-762

ORIGINAL ARTICLES

A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling

Junbin Qian^1,2 , Siel Olbrecht^1,2,3 , Bram Boeckx^1,2 , Hanne Vos⁴ , Damya Laoui^5,6 , Emre Etlioglu⁷ , Els Wauters^8,9 , Valentina Pomella⁷ , Sara Verbandt⁷ , Pieter Busschaert³ , Ayse Bassez^1,2 , Amelie Franken^1,2 , Marlies Vanden Bempt^1,2 , Jieyi Xiong^1,2 , Birgit Weynand¹⁰ , Yannick van Herck¹¹ , Asier Antoranz¹⁰ , 0, Francesca Maria Bosisio¹⁰ , Bernard Thienpont¹² , Giuseppe Floris¹⁰ , Ignace Vergote³ , Ann Smeets⁴ , Sabine Tejpar⁷ , Diether Lambrechts^1,2,*

¹VIB Center for Cancer Biology, Leuven, Belgium
²Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
³Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium
⁴Department of Oncology, KU Leuven, Surgical Oncology, University Hospitals Leuven, Leuven, Belgium
⁵Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
⁶Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium
⁷Laboratory of Molecular Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
⁸Respiratory Oncology Unit (Pneumology) and Leuven Lung Cancer Group, University Hospital KU Leuven, Leuven, Belgium
⁹Laboratory of Pneumology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
¹⁰Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research and University Hospitals Leuven, Department of Pathology, KU Leuven-University of Leuven, B-3000 Leuven, Belgium
¹¹Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium
¹²Laboratory for Functional Epigenetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
Correspondence: Diether Lambrechts(Diether.Lambrechts@kuleuven.vib.be)

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.

https://doi.org/10.1038/s41422-020-0355-0

FULL TEXT | PDF

Browse 889