Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment

Huy Q. Dinh (), Feng Pan, Geng Wang, Qing-Feng Huang, Claire E. Olingy, Zhi-Yong Wu, Shao-Hong Wang, Xin Xu, Xiu-E Xu, Jian-Zhong He, Qian Yang, Sandra Orsulic, Marcela Haro, Li-Yan Li, Guo-Wei Huang, Joshua J. Breunig, H. Phillip Koeffler, Catherine C. Hedrick, Li-Yan Xu (), Lin De-Chen () and En-Min Li ()
Additional contact information
Huy Q. Dinh: University of Wisconsin-Madison School of Medicine and Public Health
Feng Pan: Shantou University Medical College
Geng Wang: Guangdong Esophageal Cancer Research Institute, Shantou Sub-center
Qing-Feng Huang: Shantou University Medical College
Claire E. Olingy: La Jolla Institute for Immunology
Zhi-Yong Wu: Shantou Central Hospital
Shao-Hong Wang: Shantou Central Hospital
Xin Xu: Shantou University Medical College
Xiu-E Xu: Shantou University Medical College
Jian-Zhong He: Shantou University Medical College
Qian Yang: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
Sandra Orsulic: Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA
Marcela Haro: Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA
Li-Yan Li: Shantou University Medical College
Guo-Wei Huang: Shantou University Medical College
Joshua J. Breunig: Cedars-Sinai Medical Center
H. Phillip Koeffler: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
Catherine C. Hedrick: La Jolla Institute for Immunology
Li-Yan Xu: Shantou University Medical College
Lin De-Chen: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
En-Min Li: Shantou University Medical College

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

Date: 2021
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DOI: 10.1038/s41467-021-27599-5

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