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

Shanzhao Jin1 , Ruoyan Li1 , Ming-Yuan Chen2,3 , Chao Yu1 , Lin-Quan Tang2,3 , Yan-Min Liu2 , Jiang-Ping Li2 , Yi-Na Liu2 , Yi-Ling Luo2 , Yifan Zhao1 , Yu Zhang4 , Tian-Liang Xia2 , Shang-Xin Liu2 , Qi Liu2 , Guan-Nan Wang2 , Rui You2,3 , Jing-Yun Peng2,3 , Jiang Li2 , Feng Han2,5 , Jianwei Wang2,5 , Qiu-Yan Chen2,3 , Li Zhang2 , Hai-Qiang Mai2,3 , Benjamin E. Gewurz6 , Bo Zhao6 , Lawrence S. Young7 , Qian Zhong2,* , Fan Bai1,8,* , Mu-Sheng Zeng2,*

1Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University, Beijing 100871, China
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, Guangdong 510060, China
3Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
4Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
5Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
6Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
7Warwick Medical School, University of Warwick, Coventry, UK
8Center for Translational Cancer Research, First Hospital, Peking University, Beijing 100871, China
These authors contributed equally: Shanzhao Jin, Ruoyan Li, Ming-Yuan Chen, Chao Yu, Lin-Quan Tang
* Correspondence: Qian Zhong(zhongqian@sysucc.org.cn)Fan Bai(fbai@pku.edu.cn)Mu-Sheng Zeng(zengmsh@sysucc.org.cn)

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.

https://doi.org/10.1038/s41422-020-00402-8

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