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

Author

Listed:
  • Huy Q. Dinh

    (University of Wisconsin-Madison School of Medicine and Public Health
    La Jolla Institute for Immunology)

  • Feng Pan

    (Shantou University Medical College
    Guangdong Esophageal Cancer Research Institute, Shantou Sub-center)

  • Geng Wang

    (Guangdong Esophageal Cancer Research Institute, Shantou Sub-center
    Cancer Hospital of Shantou University Medical College)

  • Qing-Feng Huang

    (Shantou University Medical College
    Guangdong Esophageal Cancer Research Institute, Shantou Sub-center)

  • 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
    Guangdong Esophageal Cancer Research Institute, Shantou Sub-center)

  • Xiu-E Xu

    (Shantou University Medical College
    Guangdong Esophageal Cancer Research Institute, Shantou Sub-center)

  • Jian-Zhong He

    (Shantou University Medical College
    Guangdong Esophageal Cancer Research Institute, Shantou Sub-center)

  • 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
    Guangdong Esophageal Cancer Research Institute, Shantou Sub-center)

  • De-Chen Lin

    (Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center)

  • En-Min Li

    (Shantou University Medical College
    Guangdong Esophageal Cancer Research Institute, Shantou Sub-center)

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.

Suggested Citation

  • 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, 2021. "Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27599-5
    DOI: 10.1038/s41467-021-27599-5
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    Cited by:

    1. De-Chen Lin, 2023. "Large-scale genomic analyses reveal alterations and mechanisms underlying clonal evolution and immune evasion in esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-3, December.
    2. Zhenlin Yang & He Tian & Xiaowei Chen & Bozhao Li & Guangyu Bai & Qingyuan Cai & Jiachen Xu & Wei Guo & Shuaibo Wang & Yue Peng & Qing Liang & Liyan Xue & Shugeng Gao, 2024. "Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Yuan Jiang & Yueyuan Zheng & Yuan-Wei Zhang & Shuai Kong & Jinxiu Dong & Fei Wang & Benjamin Ziman & Sigal Gery & Jia-Jie Hao & Dan Zhou & Jianian Zhou & Allen S. Ho & Uttam K. Sinha & Jian Chen & Shu, 2024. "Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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