Single cell RNA-seq reveals the CCL5/SDC1 receptor-ligand interaction between T cells and tumor cells in pancreatic cancer

被引:72
作者
Chen, Kai [1 ]
Wang, Yazhou [2 ]
Hou, Yuting [1 ]
Wang, Qi [1 ]
Long, Di [1 ]
Liu, Xinxin [1 ]
Tian, Xiaodong [1 ,3 ]
Yang, Yinmo [1 ,3 ]
机构
[1] Peking Univ First Hosp, Dept Gen Surg, Beijing 100034, Peoples R China
[2] Nanjing Med Univ, Pancreas Ctr, Affiliated Hosp 1, Nanjing 210029, Peoples R China
[3] Peking Univ First Hosp, Dept Gen Surg, 8th Xishiku St, Beijing 100034, Peoples R China
基金
北京市自然科学基金; 中国国家自然科学基金;
关键词
ScRNA-seq; Heterogeneity; Crosstalk; CCL5; T cell development; LANDSCAPE; RANTES;
D O I
10.1016/j.canlet.2022.215834
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the complex tumor microenvironment (TME), consisting of an abundance of stromal cells. Among them, tumor infiltrating T cells play a pivotal role in tumor progress. To identify the full spectrum and developmental trajectory of T cells and their crosstalk with tumor cells in PDAC, we conducted scRNA-seq analysis based on multiple datasets from our institution and open da-tabases. We delineated the cellular landscape and transcriptional dynamics of T cells in PDAC. Through the inferCNV analysis and known tumor markers, the malignant ductal cells were identified. The inter-patients heterogeneity of tumor cells was also identified. After integrating T cells and malignant ductal cells, we found the CCL5-SDC1/4 receptor-ligand interactions between them. Furthermore, we demonstrated that CCL5 pro-moted tumor cells migration via interacting with SDC1 in vitro. Our findings pave the way for characterizing the heterogeneity and development trajectory of T cells, and cell-to-cell communications in TME of PDAC, which might provide a new target for immunotherapy.
引用
收藏
页数:12
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