Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma

Autor: Shanzhao Jin, Yi-Ling Luo, Shang-Xin Liu, Mu Sheng Zeng, Jiang-Ping Li, Jing-Yun Peng, Ruoyan Li, Yan-Min Liu, Guan-Nan Wang, Jianwei Wang, Bo Zhao, Lin-Quan Tang, Ming-Yuan Chen, Tian-Liang Xia, Yi-Na Liu, Rui You, Feng Han, Chao Yu, Jiang Li, Fan Bai, Hai-Qiang Mai, Qiu-Yan Chen, Lawrence S. Young, Y Y Zhao, Qi Liu, Li Zhang, Yu Zhang, Qian Zhong, Benjamin E. Gewurz
Rok vydání: 2020
Předmět:
Zdroj: Cell Res
ISSN: 1748-7838
1001-0602
DOI: 10.1038/s41422-020-00402-8
Popis: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a complex tumor ecosystem. How the interplay between tumor cells, EBV, and the microenvironment contributes to NPC progression and immune evasion remains unclear. Here we performed single-cell RNA sequencing on ~104,000 cells from 19 EBV(+) NPCs and 7 nonmalignant nasopharyngeal biopsies, simultaneously profiling the transcriptomes of malignant cells, EBV, stromal and immune cells. Overall, we identified global upregulation of interferon responses in the multicellular ecosystem of NPC. Notably, an epithelial–immune dual feature of malignant cells was discovered and associated with poor prognosis. Functional experiments revealed that tumor cells with this dual feature exhibited a higher capacity for tumorigenesis. Further characterization of the cellular components of the tumor microenvironment (TME) and their interactions with tumor cells revealed that the dual feature of tumor cells was positively correlated with the expression of co-inhibitory receptors on CD8(+) tumor-infiltrating T cells. In addition, tumor cells with the dual feature were found to repress IFN-γ production by T cells, demonstrating their capacity for immune suppression. Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.
Databáze: OpenAIRE
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