Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma.

Autor:	Sharma A; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore. Electronic address: sharmaa@gis.a-star.edu.sg., Seow JJW; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore., Dutertre CA; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore; Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore., Pai R; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore., Blériot C; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore., Mishra A; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore., Wong RMM; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore., Singh GSN; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore., Sudhagar S; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore., Khalilnezhad S; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore., Erdal S; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore., Teo HM; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore., Khalilnezhad A; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore., Chakarov S; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore., Lim TKH; Department of Pathology, Singapore General Hospital, Singapore 169608, Singapore., Fui ACY; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore., Chieh AKW; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University of Hospital, Singapore 119074, Singapore., Chung CP; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore., Bonney GK; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University of Hospital, Singapore 119074, Singapore., Goh BK; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore., Chan JKY; Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore; Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, NUS, Singapore 117597, Singapore; Academic Clinical Program in Obstetrics and Gynaecology, Duke-NUS Medical School, Singapore 169857, Singapore., Chow PKH; Division of Surgery and Surgical Oncology, National Cancer Centre, Singapore 169610, Singapore; Academic Clinical Programme for Surgery, Duke-NUS Medical School, Singapore 169857, Singapore. Electronic address: pierce.chow.k.h@singhealth.com.sg., Ginhoux F; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3 and 4, Singapore 138648, Singapore; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore 169856, Singapore. Electronic address: florent_ginhoux@immunol.a-star.edu.sg., DasGupta R; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore. Electronic address: dasguptar@gis.a-star.edu.sg.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 Oct 15; Vol. 183 (2), pp. 377-394.e21. Date of Electronic Publication: 2020 Sep 24.
DOI:	10.1016/j.cell.2020.08.040
Abstrakt:	We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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