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单细胞 RNA 测序揭示鼻咽癌中肿瘤和浸润免疫细胞的全景。

Single cell RNA-seq reveals the landscape of tumor and infiltrating immune cells in nasopharyngeal carcinoma.

机构信息

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.

Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.

出版信息

Cancer Lett. 2020 May 1;477:131-143. doi: 10.1016/j.canlet.2020.02.010. Epub 2020 Feb 13.

Abstract

Nasopharyngeal carcinoma (NPC) is one of the most malignant tumors in Southern China and southeast Asia, which is characterized by a dense lymphocyte infiltration and a poor prognosis. The emergence of single-cell sequencing represents a powerful tool to resolve tumor heterogeneity and delineate the complex communication among the tumor cells with neighboring stromal and immune cells in the tumor microenvironment (TME). Here, we performed single cell RNA-seq and analyzed tumor cells together with the infiltrating immune cells from three NPC tumor tissues. In our study, the malignant cells display the intra- and inter-tumoral heterogeneity among the individual patients. Analysis of the immune cells reveal the heterogeneous composition of the distinct immune cells and the various functional states of T cells in NPC tumors. Additionally, coupled with the reconstruct of the T cell receptor (TCR) sequences from immune cells full-length single-cell sequence data, we identify the diverse T cell clonotypes and expansion distribution in individual tumors. Overall, we firstly reveal the landscape of tumor and infiltrating immune cells in nasopharyngeal cancer. These results provide deeper insights on the mechanisms of tumor clearance by immune cells in the surrounding microenvironment, which will be helpful in improving the targeted and immune therapies for NPC.

摘要

鼻咽癌(NPC)是中国南方和东南亚地区最恶性的肿瘤之一,其特征是淋巴细胞浸润密集,预后不良。单细胞测序的出现代表了一种强大的工具,可以解决肿瘤异质性,并描绘肿瘤微环境(TME)中肿瘤细胞与邻近基质和免疫细胞之间的复杂通讯。在这里,我们对来自三个 NPC 肿瘤组织的肿瘤细胞和浸润免疫细胞进行了单细胞 RNA-seq 分析。在我们的研究中,恶性细胞显示出个体患者之间的肿瘤内和肿瘤间异质性。免疫细胞分析揭示了不同免疫细胞的异质组成以及 NPC 肿瘤中 T 细胞的各种功能状态。此外,通过对免疫细胞全长单细胞序列数据的 T 细胞受体(TCR)序列进行重建,我们在单个肿瘤中鉴定出多样化的 T 细胞克隆型和扩增分布。总的来说,我们首次揭示了鼻咽癌中肿瘤和浸润免疫细胞的全景。这些结果为了解周围微环境中免疫细胞清除肿瘤的机制提供了更深入的见解,这将有助于提高针对 NPC 的靶向和免疫治疗。

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