Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma

Lanqi Gong, Dora Lai-Wan Kwong, Wei Dai, Pingan Wu, Shanshan Li, Qian Yan, Yu Zhang, Baifeng Zhang, Xiaona Fang, Li Liu, Min Luo, Beilei Liu, Larry Ka-Yue Chow, Qingyun Chen, Jinlin Huang, Victor Ho-Fun Lee, Ka-On Lam, Anthony Wing-Ip Lo, Zhiwei Chen, Yan Wang, Anne Wing-Mui Lee and Xin-Yuan Guan ()
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Lanqi Gong: The University of Hong Kong-Shenzhen Hospital
Dora Lai-Wan Kwong: The University of Hong Kong-Shenzhen Hospital
Wei Dai: The University of Hong Kong-Shenzhen Hospital
Pingan Wu: The University of Hong Kong-Shenzhen Hospital
Shanshan Li: The University of Hong Kong-Shenzhen Hospital
Qian Yan: The University of Hong Kong-Shenzhen Hospital
Yu Zhang: The University of Hong Kong
Baifeng Zhang: The University of Hong Kong
Xiaona Fang: The University of Hong Kong
Li Liu: The University of Hong Kong
Min Luo: The University of Hong Kong-Shenzhen Hospital
Beilei Liu: The University of Hong Kong
Larry Ka-Yue Chow: The University of Hong Kong
Qingyun Chen: Sun Yat-sen University Cancer Center
Jinlin Huang: The University of Hong Kong
Victor Ho-Fun Lee: The University of Hong Kong-Shenzhen Hospital
Ka-On Lam: The University of Hong Kong-Shenzhen Hospital
Anthony Wing-Ip Lo: The University of Hong Kong
Zhiwei Chen: The University of Hong Kong
Yan Wang: The University of Hong Kong-Shenzhen Hospital
Anne Wing-Mui Lee: The University of Hong Kong-Shenzhen Hospital
Xin-Yuan Guan: The University of Hong Kong-Shenzhen Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.

Date: 2021
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DOI: 10.1038/s41467-021-21795-z

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