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.
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The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA000087 (accessible at http://bigd.big.ac.cn/gsa-human). Code is available from the corresponding author on reasonable request.
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This work was financially supported by the National Key R&D Program (2017YFA0505604), the National Science and Technology Major Project (2019YFC1315702, 2018ZX10302205), the National Natural Science Foundation of China (31722003, 81520108022, 31770925, 81621004, 81830090, 81772883, 81772895, 81602371, and 81230045), Guangdong Province Key Research and Development Program (2019B020226002), Natural Science Foundation of Guangdong Province (2017A030312003), and Guangzhou Science Technology and Innovation Commission (201607020038). R.L. was supported by the Postdoctoral Fellowship of Bo Ya. We thank Fei Wang from the National Center for Protein Sciences Beijing (Peking University) and Shupeng Chen from SYSUCC for assistance with FACS. The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval number RDDB2020000935.
The authors declare no competing interests.
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Jin, S., Li, R., Chen, M. et al. Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma. Cell Res (2020). https://doi.org/10.1038/s41422-020-00402-8