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Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment

Author

Listed:
  • Yingxia Zheng

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Zheyi Chen

    (Shanghai Jiao Tong University School of Medicine)

  • Yichao Han

    (Shanghai Jiao Tong University School of Medicine)

  • Li Han

    (Shanghai Jiao Tong University School of Medicine)

  • Xin Zou

    (Shanghai Jiao Tong University)

  • Bingqian Zhou

    (Shanghai Jiao Tong University School of Medicine)

  • Rui Hu

    (Shanghai Jiao Tong University School of Medicine)

  • Jie Hao

    (Shanghai Jiao Tong University)

  • Shihao Bai

    (Shanghai Jiao Tong University)

  • Haibo Xiao

    (Shanghai Jiao Tong University School of Medicine)

  • Wei Vivian Li

    (Rutgers School of Public Health)

  • Alex Bueker

    (Rutgers Cancer Institute of New Jersey)

  • Yanhui Ma

    (Shanghai Jiao Tong University School of Medicine)

  • Guohua Xie

    (Shanghai Jiao Tong University School of Medicine)

  • Junyao Yang

    (Shanghai Jiao Tong University School of Medicine)

  • Shiyu Chen

    (Shanghai Jiao Tong University School of Medicine)

  • Hecheng Li

    (Shanghai Jiao Tong University School of Medicine)

  • Jian Cao

    (Rutgers Cancer Institute of New Jersey
    Robert Wood Johnson Medical School, Rutgers University)

  • Lisong Shen

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

Abstract

Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.

Suggested Citation

  • Yingxia Zheng & Zheyi Chen & Yichao Han & Li Han & Xin Zou & Bingqian Zhou & Rui Hu & Jie Hao & Shihao Bai & Haibo Xiao & Wei Vivian Li & Alex Bueker & Yanhui Ma & Guohua Xie & Junyao Yang & Shiyu Che, 2020. "Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20019-0
    DOI: 10.1038/s41467-020-20019-0
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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. Xuejiao Liu & Simin Zhao & Keke Wang & Liting Zhou & Ming Jiang & Yunfeng Gao & Ran Yang & Shiwen Yan & Wen Zhang & Bingbing Lu & Feifei Liu & Ran Zhao & Wenting Liu & Zihan Zhang & Kangdong Liu & Xia, 2023. "Spatial transcriptomics analysis of esophageal squamous precancerous lesions and their progression to esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Felix Drost & Yang An & Irene Bonafonte-Pardàs & Lisa M. Dratva & Rik G. H. Lindeboom & Muzlifah Haniffa & Sarah A. Teichmann & Fabian Theis & Mohammad Lotfollahi & Benjamin Schubert, 2024. "Multi-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. 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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