PT  - JOURNAL ARTICLE
AU  - Junbin Qian
AU  - Siel Olbrecht
AU  - Bram Boeckx
AU  - Hanne Vos
AU  - Damya Laoui
AU  - Emre Etlioglu
AU  - Els Wauters
AU  - Valentina Pomella
AU  - Sara Verbandt
AU  - Pieter Busschaert
AU  - Ayse Bassez
AU  - Amelie Franken
AU  - Marlies Vanden Bempt
AU  - Jieyi Xiong
AU  - Birgit Weynand
AU  - Yannick van Herck
AU  - Asier Antoranz
AU  - Francesca Maria Bosisio
AU  - Bernard Thienpont
AU  - Giuseppe Floris
AU  - Ignace Vergote
AU  - Ann Smeets
AU  - Sabine Tejpar
AU  - Diether Lambrechts
TI  - A Pan-cancer Blueprint of the Heterogeneous Tumour Microenvironment Revealed by Single-Cell Profiling
AID  - 10.1101/2020.04.01.019646
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.01.019646
4099  - http://biorxiv.org/content/early/2020/04/02/2020.04.01.019646.short
4100  - http://biorxiv.org/content/early/2020/04/02/2020.04.01.019646.full
AB  - The stromal compartment of the tumour microenvironment consists of a heterogeneous set of tissue-resident and tumour-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 tumour-infiltrating cell types are largely shared across cancer types. Finally, by applying the blueprint to melanoma tumours 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 a first panoramic view on the shared complexity of stromal cells in different cancers.