Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.
IF: 17.694
Cited by: 62


Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.


Gene Expression

MeSH terms

Biomarkers, Tumor
Carcinoma, Hepatocellular
Cell Cycle
Cell Line, Tumor
Chemokine CCL5
Gene Expression Regulation, Neoplastic
Genetic Heterogeneity
Immune Evasion
Liver Neoplasms
Mice, Inbred C57BL
Middle Aged
Neoplasm Metastasis
Neoplastic Cells, Circulating
Tumor Microenvironment


Sun, Yun-Fan
Wu, Liang
Liu, Shi-Ping
Jiang, Miao-Miao
Hu, Bo
Zhou, Kai-Qian
Guo, Wei
Xu, Yang
Zhong, Yu
Zhou, Xiao-Rui
Zhang, Ze-Fan
Liu, Geng
Liu, Sheng
Shi, Ying-Hong
Ji, Yuan
Du, Min
Li, Nan-Nan
Li, Gui-Bo
Zhao, Zhi-Kun
Huang, Xiao-Yun
Xu, Li-Qin
Yu, Qi-Chao
Peng, David H
Qiu, Shuang-Jian
Sun, Hui-Chuan
Dean, Michael
Wang, Xiang-Dong
Chung, Wen-Yuan
Dennison, Ashley R
Zhou, Jian
Hou, Yong
Fan, Jia
Yang, Xin-Rong

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