Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer
Top Cited Papers
- 25 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 52 (6), 594-603
- https://doi.org/10.1038/s41588-020-0636-z
Abstract
Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.Keywords
Funding Information
- National Research Foundation of Korea (NRF-2017M3A9A7050803)
- Stichting Tegen Kanker (2018-127, 2016-133)
- S.T is supported as a Senior Clinical Investigator by the Research Foundation - Flanders (FWO).
This publication has 75 references indexed in Scilit:
- A colorectal cancer classification system that associates cellular phenotype and responses to therapyNature Medicine, 2013
- Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis InitiationCancer Cell, 2012
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- Single-cell dissection of transcriptional heterogeneity in human colon tumorsNature Biotechnology, 2011
- Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cellsLeukemia, 2011
- A framework for variation discovery and genotyping using next-generation DNA sequencing dataNature Genetics, 2011
- Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epitheliumThe Journal of cell biology, 2011
- Fast and accurate long-read alignment with Burrows–Wheeler transformBioinformatics, 2010
- PANTHER Pathway: An Ontology-Based Pathway Database Coupled with Data Analysis ToolsPublished by Springer Science and Business Media LLC ,2009
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005