Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer.

Lee HO; Hong Y; Etlioglu HE; Cho YB; Pomella V; Van den Bosch B; Vanhecke J; Verbandt S; Hong H; Min JW; Kim N; Eum HH; Qian J; Boeckx B; Lambrechts D; Tsantoulis P; De Hertogh G; Chung W; Lee T; An M; Shin HT; Joung JG; Jung MH; Ko G; Wirapati P; Kim SH; Kim HC; Yun SH; Tan IBH; Ranjan B; Lee WY; Kim TY; Choi JK; Kim YJ; Prabhakar S; Tejpar S; Park WY

doi:10.1038/s41588-020-0636-z

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Journal article

Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer.

Lee HO Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Hong Y Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Etlioglu HE Molecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Cho YB Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea.
Pomella V Molecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Van den Bosch B Molecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Vanhecke J Molecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Verbandt S Molecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Hong H Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Min JW Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Kim N Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Eum HH Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Qian J Center for Cancer Biology, VIB, Leuven, Belgium.
Boeckx B Center for Cancer Biology, VIB, Leuven, Belgium.
Lambrechts D Center for Cancer Biology, VIB, Leuven, Belgium.
Tsantoulis P Centre d'Oncologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
De Hertogh G Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
Chung W Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Lee T Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
An M Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Shin HT Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Joung JG Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Jung MH Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, Korea.
Ko G Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Wirapati P Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Kim SH Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim HC Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yun SH Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Tan IBH Division of Medical Oncology, National Cancer Center, Singapore, Singapore.
Ranjan B Systems Biology and Data Analytics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Lee WY Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim TY Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Choi JK Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Kim YJ Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, Korea.
Prabhakar S Systems Biology and Data Analytics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Tejpar S Molecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium. sabine.tejpar@uzleuven.be.
Park WY Samsung Genome Institute, Samsung Medical Center, Seoul, Korea. woongyang.park@samsung.com.

2020-05-27

Published in:

Nature genetics. - 2020

Gene Expression Regulation, Neoplastic

English 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.

Language

English

Open access status

closed

Identifiers

DOI 10.1038/s41588-020-0636-z
PMID 32451460

Persistent URL

https://sonar.ch/global/documents/137935

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Journal article

Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer.

Cell Lineage

Colorectal Neoplasms

Gastric Mucosa

Gene Expression Regulation, Neoplastic

Humans

Sequence Analysis, RNA

Single-Cell Analysis

Stromal Cells

T-Lymphocytes

Tumor Microenvironment

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