Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma.
Journalcell research20.507Date
2020 Jul 20
24 days ago
Publication Type
Journal Article
2020-Jul-20 / :
Chen YP 1, Yin JH 2, Li WF 1, Li HJ 3, Chen DP 1, 4, Zhang CJ 2, Lv JW 1, Wang YQ 1, Li XM 1, Li JY 1, Zhang PP 1, Li YQ 1, He QM 1, Yang XJ 1, Lei Y 1, Tang LL 1, Zhou GQ 1, Mao YP 1, Wei C 2, Xiong KX 2, Zhang HB 5, Zhu SD 2, Hou Y 2, Sun Y 1, Dean M 6, Amit I 7, Wu K 2, Kuang DM 1, 4, Li GB 2, 8, Liu N 1, Ma J 9
  • 2. BGI-Shenzhen, Shenzhen, Guangdong, 518120, China.
  • 3. CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
  • 4. MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510275, China.
  • 5. Key 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.
  • 6. Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA.
  • 7. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • 8. Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen, Guangdong, 518120, China.
  • 9. Department 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. [email protected]
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.
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