Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution

• Published in: Nature communications Vol. 12; no. 1; pp. 741 - 18
• Main Authors: Liu, Yang, He, Shuai, Wang, Xi-Liang, Peng, Wan, Chen, Qiu-Yan, Chi, Dong-Mei, Chen, Jie-Rong, Han, Bo-Wei, Lin, Guo-Wang, Li, Yi-Qi, Wang, Qian-Yu, Peng, Rou-Jun, Wei, Pan-Pan, Guo, Xiang, Li, Bo, Xia, Xiaojun, Mai, Hai-Qiang, Hu, Xue-Da, Zhang, Zemin, Zeng, Yi-Xin, Bei, Jin-Xin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 631/250/580; 631/67/1536; 631/67/2329; 631/67/327; 82/51; 96/31; Cancer; CD8 antigen; CD8-Positive T-Lymphocytes - enzymology; CD8-Positive T-Lymphocytes - metabolism; Cell interactions; Cells, Cultured; CX3CR1 protein; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Epstein-Barr virus; Gene expression; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - metabolism; Heterogeneity; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; Humans; Lymphocytes; Lymphocytes T; Male; Microenvironments; multidisciplinary; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - immunology; Nasopharyngeal Carcinoma - metabolism; Science; Science (multidisciplinary); T cell receptors; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Throat cancer; Trajectory analysis; Transcriptomes; Tumor microenvironment; Tumor Microenvironment - immunology; Tumor Microenvironment - physiology; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21043-4

The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8 + T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8 + T and immune-suppressive TNFRSF4 + Treg cells in tumours might derive from peripheral CX3CR1 + CD8 + T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3 + DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3 + DCs, Treg, exhausted CD8 + T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC. Nasopharyngeal carcinoma is a diverse cancer characterised by a heterogeneous microenvironment. Here, the authors use single cell sequencing to analyse the tumour microenvironment in 10 nasopharyngeal carcinoma tumours and identify different cell types including immune-suppressive T regulatory, tolerogenic dendritic, and exhausted CD8 T cells.