1. Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma
- Author
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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, and Benjamin E. Gewurz
- Subjects
Stromal cell ,T-Lymphocytes ,Mice, Nude ,Cell Communication ,Biology ,Ligands ,medicine.disease_cause ,Article ,Immunomodulation ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Interferon ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Myeloid Cells ,Molecular Biology ,Cell Aggregation ,030304 developmental biology ,Mice, Inbred BALB C ,Stochastic Processes ,0303 health sciences ,Tumor microenvironment ,Gene Expression Profiling ,Nasopharyngeal Neoplasms ,Cell Biology ,Fibroblasts ,medicine.disease ,Cell aggregation ,Gene Expression Regulation, Neoplastic ,Nasopharyngeal carcinoma ,Virus Diseases ,Cancer research ,Female ,Interferons ,Single-Cell Analysis ,Stromal Cells ,Carcinogenesis ,030217 neurology & neurosurgery ,CD8 ,medicine.drug - Abstract
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.
- Published
- 2020