Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma

Yun-Fan Sun, Liang Wu, Shi-Ping Liu, Miao-Miao Jiang, Bo Hu, Kai-Qian Zhou, Wei Guo, Yang Xu, Yu Zhong, Xiao-Rui Zhou, Ze-Fan Zhang, Geng Liu, Sheng Liu, Ying-Hong Shi, Yuan Ji, Min Du, Nan-Nan Li, Gui-Bo Li, Zhi-Kun Zhao, Xiao-Yun Huang, Li-Qin Xu, Qi-Chao Yu, David H. Peng, Shuang-Jian Qiu, Hui-Chuan Sun, Michael Dean, Xiang-Dong Wang, Wen-Yuan Chung, Ashley R. Dennison, Jian Zhou, Yong Hou (), Jia Fan () and Xin-Rong Yang ()
Additional contact information
Yun-Fan Sun: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Liang Wu: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Shi-Ping Liu: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Miao-Miao Jiang: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Bo Hu: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Kai-Qian Zhou: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Wei Guo: Fudan University
Yang Xu: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Yu Zhong: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Xiao-Rui Zhou: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Ze-Fan Zhang: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Geng Liu: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Sheng Liu: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Ying-Hong Shi: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Yuan Ji: Fudan University
Min Du: Fudan University
Nan-Nan Li: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Gui-Bo Li: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Zhi-Kun Zhao: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Xiao-Yun Huang: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Li-Qin Xu: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
Qi-Chao Yu: BGI-Shenzhen, Shenzhen, Beishan Industrial Zone
David H. Peng: Dunwill Med-Tech
Shuang-Jian Qiu: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Hui-Chuan Sun: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Michael Dean: National Cancer Institute Gaithersburg
Xiang-Dong Wang: Fudan University Center for Clinical Bioinformatics
Wen-Yuan Chung: University Hospitals of Leicester NHS Trust
Ashley R. Dennison: University Hospitals of Leicester NHS Trust
Jian Zhou: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Yong Hou: Fudan University–BGI
Jia Fan: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
Xin-Rong Yang: Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24386-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24386-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24386-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().