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

Single cell RNA-seq reveals the landscape of tumor and infiltrating immune cells in nasopharyngeal carcinoma
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单细胞 RNA-seq 揭示鼻咽癌肿瘤和浸润免疫细胞的概况

DOI:
10.1016/j.canlet.2020.02.010
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发表时间:
2020-05-01
期刊:
影响因子:
9.7
通讯作者:
Zeng, Zhaoyang
Zeng, Zhaoyang
中科院分区:
医学1区
文献类型:
--
作者:
Zhao, Jin;Guo, Can;Zeng, Zhaoyang

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鼻咽癌(Nasopharyngeal carcinoma,NPC)是我国南方及东南亚地区最常见的恶性肿瘤之一,以淋巴细胞密集浸润为特征,预后差。单细胞测序的出现代表了解决肿瘤异质性和描绘肿瘤微环境(TME)中肿瘤细胞与相邻基质和免疫细胞之间的复杂通信的强大工具。在这里,我们进行了单细胞RNA-seq,并分析了肿瘤细胞以及来自三种NPC肿瘤组织的浸润性免疫细胞。在我们的研究中,恶性细胞在个体患者中显示出肿瘤内和肿瘤间的异质性。免疫细胞的分析揭示了NPC肿瘤中不同免疫细胞的异质性组成和T细胞的各种功能状态。此外,结合从免疫细胞全长单细胞序列数据重建的T细胞受体(TCR)序列,我们确定了个体肿瘤中不同的T细胞克隆型和扩增分布。总体而言,我们首次揭示了鼻咽癌中肿瘤和浸润免疫细胞的景观。这些结果为深入了解免疫细胞在周围微环境中清除肿瘤的机制提供了更深层次的见解,这将有助于改善NPC的靶向和免疫治疗。
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.