Volume 30, No 11, Nov 2020

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 30 Issue 11, November 2020: 950-965

ORIGINAL ARTICLES

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

Shanzhao Jin¹ , Ruoyan Li¹ , Ming-Yuan Chen^2,3 , Chao Yu¹ , Lin-Quan Tang^2,3 , 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 You^2,3 , Jing-Yun Peng^2,3 , Jiang Li² , Feng Han^2,5 , Jianwei Wang^2,5 , Qiu-Yan Chen^2,3 , Li Zhang² , Hai-Qiang Mai^2,3 , Benjamin E. Gewurz⁶ , Bo Zhao⁶ , Lawrence S. Young⁷ , Qian Zhong^2,* , Fan Bai^1,8,* , Mu-Sheng Zeng^2,*

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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