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, Lisong Shen

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Article number6268
JournalNature communications
Issue number1
StatePublished - Dec 2020

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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