| Title | Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma |
| Authors | Jin, Shanzhao Li, Ruoyan Chen, Ming-Yuan Yu, Chao Tang, Lin-Quan Liu, Yan-Min Li, Jiang-Ping Liu, Yi-Na Luo, Yi-Ling Zhao, Yifan Zhang, Yu Xia, Tian-Liang Liu, Shang-Xin Liu, Qi Wang, Guan-Nan You, Rui Peng, Jing-Yun Li, Jiang Han, Feng Wang, Jianwei Chen, Qiu-Yan Zhang, Li Mai, Hai-Qiang Gewurz, Benjamin E. Zhao, Bo Young, Lawrence S. Zhong, Qian Bai, Fan Zeng, Mu-Sheng |
| Affiliation | Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Beijing 100871, Peoples R China Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China Sun Yat Sen Univ, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Collaborat Innovat Ctr Canc Med, Canc Ctr SYSUCC,State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China Sun Yat Sen Univ, Canc Ctr, Dept Nasopharyngeal Carcinoma, Guangzhou 510060, Guangdong, Peoples R China Sun Yat Sen Univ, Dept Pathol, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China Sun Yat Sen Univ, Dept Ultrasound, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England Peking Univ, Hosp 1, Ctr Translat Canc Res, Beijing 100871, Peoples R China |
| Keywords | EPSTEIN-BARR-VIRUS MHC CLASS-II GENOME-WIDE ASSOCIATION RNA-SEQ INFILTRATING LYMPHOCYTES READ ALIGNMENT EXPRESSION GENE ESTABLISHMENT PATHOGENESIS |
| Issue Date | Sep-2020 |
| Publisher | CELL RESEARCH |
| 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 similar to 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-gamma 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. |
| URI | http://hdl.handle.net/20.500.11897/607619 |
| ISSN | 1001-0602 |
| DOI | 10.1038/s41422-020-00402-8 |
| Indexed | SCI(E) |
| Appears in Collections: | 生物医学前沿创新中心 生命科学学院 第一医院 |
