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: 1024-1042   |  Open Access

ORIGINAL ARTICLES

Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma

Yu-Pei Chen^1,† , Jian-Hua Yin^2,† , Wen-Fei Li^1,† , Han-Jie Li^3,† , Dong-Ping Chen^1,4,† , Cui-Juan Zhang^2,† , Jia-Wei Lv¹ , Ya-Qin Wang¹ , Xiao-Min Li¹ , Jun-Yan Li¹ , Pan-Pan Zhang¹ , Ying-Qin Li¹ , Qing-Mei He¹ , Xiao-Jing Yang¹ , Yuan Lei¹ , Ling-Long Tang¹ , Guan-Qun Zhou¹ , Yan-Ping Mao¹ , Chen Wei² , Ke-Xu Xiong² , Hong-Bo Zhang⁵ , Shi-Da Zhu² , Yong Hou² , Ying Sun¹ , Michael Dean⁶ , Ido Amit⁷ , Kui Wu² , Dong-Ming Kuang^1,4 , Gui-Bo Li^2,8 , Na Liu¹ , Jun Ma^1,*

¹Department of Radiation Oncology, State 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, Guangzhou, Guangdong 510060, China
²BGI-Shenzhen, Shenzhen, Guangdong 518120, China
³CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China
⁴MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
⁵Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education and The Department of Histology and Embryology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
⁶Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA
⁷Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
⁸Shenzhen Key Laboratory of Single-Cell Omics, BGIShenzhen, Shenzhen, Guangdong 518120, China
^†These authors contributed equally
These senior authors jointly directed this work: Kui Wu, Dong-Ming Kuang, Gui-Bo Li, Na Liu, Jun Ma Correspondence: Jun Ma(majun2@mail.sysu.edu.cn)

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A+ dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell–cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A+ DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.

https://doi.org/10.1038/s41422-020-0374-x

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