Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment

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 Chen, Hecheng Li (), Jian Cao () and Lisong Shen ()
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Yingxia Zheng: 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
Lisong Shen: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20019-0

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