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Nat Commun. 2017 May 5;8:15081. doi: 10.1038/ncomms15081.

Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer.

Chung W1,2, Eum HH1,3, Lee HO1,4, Lee KM5,6, Lee HB5,7, Kim KT1, Ryu HS8, Kim S9, Lee JE9, Park YH10, Kan Z11, Han W5,7, Park WY1,2,4.

Author information

1
Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
2
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences &Technology, Sungkyunkwan University, Seoul 06351, Korea.
3
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
4
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
5
Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
6
Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea.
7
Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea.
8
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, South Korea.
9
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
10
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul 06351, Korea.
11
Oncology Research, Pfizer Inc., San Diego, California 92121, USA.

Abstract

Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways. Most of the non-cancer cells are immune cells, with three distinct clusters of T lymphocytes, B lymphocytes and macrophages. T lymphocytes and macrophages both display immunosuppressive characteristics: T cells with a regulatory or an exhausted phenotype and macrophages with an M2 phenotype. These results illustrate that the breast cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by the tumour cells and immune cells in the surrounding microenvironment.

PMID:
28474673
PMCID:
PMC5424158
DOI:
10.1038/ncomms15081
[Indexed for MEDLINE]
Free PMC Article

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