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A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular Carcinoma

91 Pages Posted: 30 Jun 2020 Publication Status: Review Complete

See all articles by Yiming Lu

Yiming Lu

National Center for Protein Sciences - State Key Laboratory of Proteomics

Aiqing Yang

National Center for Protein Sciences - State Key Laboratory of Proteomics

Cheng Quan

National Center for Protein Sciences - State Key Laboratory of Proteomics

Haoyun Zhang

Chinese PLA General Hospital - Department of Hepatobiliary Surgery

Yingwei Pan

Chinese PLA General Hospital - Department of Hepatobiliary Surgery

Yuanfeng Li

National Center for Protein Sciences - State Key Laboratory of Proteomics

Chengming Gao

National Center for Protein Sciences - State Key Laboratory of Proteomics

Hao Lu

National Center for Protein Sciences - State Key Laboratory of Proteomics

Pengbo Cao

National Center for Protein Sciences - State Key Laboratory of Proteomics

Hongxia Chen

National Center for Protein Sciences - State Key Laboratory of Proteomics

Shichun Lu

Chinese PLA General Hospital - Department of Hepatobiliary Surgery

Gangqiao Zhou

National Center for Protein Sciences - State Key Laboratory of Proteomics

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Abstract

Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generated a single-cell atlas of the multicellular ecosystem of HCCs from four relevant sites. Antitumor central memory T (TCM) cells were found in tertiary lymphoid structures (TLSs). Chronic HBV/HCV infection increases infiltration of CD8+ T cells in tumors but aggravates T cell exhaustion. We identified CD11b+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and two distinct differentiation trajectories contribute to their accumulation. We further demonstrated CD11b+ TAMs promote HCC cells invasion and migration, and angiogenesis. We characterized the heterogeneous subpopulations of malignant hepatocytes and their multifaceted roles in shaping the immune microenvironment. Finally, we identified seven TME subtypes that can predict patient prognosis. Collectively, this large-scale atlas deepens our understanding of the ecosystem in primary and metastatic HCCs, might facilitating the development of new immune therapy strategies for this malignancy.

Keywords: hepatocellular carcinoma, single-cell RNA sequencing, Tumor Microenvironment, Tertiary lymphoid structure, Tumor-associated macrophage

Suggested Citation

Lu, Yiming and Yang, Aiqing and Quan, Cheng and Zhang, Haoyun and Pan, Yingwei and Li, Yuanfeng and Gao, Chengming and Lu, Hao and Cao, Pengbo and Chen, Hongxia and Lu, Shichun and Zhou, Gangqiao, A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular Carcinoma. Available at SSRN: https://ssrn.com/abstract=3624436 or http://dx.doi.org/10.2139/ssrn.3624436
This version of the paper has not been formally peer reviewed.

Yiming Lu

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Aiqing Yang

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Cheng Quan

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Haoyun Zhang

Chinese PLA General Hospital - Department of Hepatobiliary Surgery

Beijing, 100853
China

Yingwei Pan

Chinese PLA General Hospital - Department of Hepatobiliary Surgery

Beijing, 100853
China

Yuanfeng Li

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Chengming Gao

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Hao Lu

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Pengbo Cao

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Hongxia Chen

National Center for Protein Sciences - State Key Laboratory of Proteomics

China

Shichun Lu

Chinese PLA General Hospital - Department of Hepatobiliary Surgery

Beijing, 100853
China

Gangqiao Zhou (Contact Author)

National Center for Protein Sciences - State Key Laboratory of Proteomics ( email )

China

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