A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

Yiming Lu, Aiqing Yang, Cheng Quan, Yingwei Pan, Haoyun Zhang, Yuanfeng Li, Chengming Gao, Hao Lu, Xueting Wang, Pengbo Cao, Hongxia Chen, Shichun Lu and Gangqiao Zhou ()
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Yiming Lu: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Aiqing Yang: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Cheng Quan: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Yingwei Pan: Chinese PLA General Hospital
Haoyun Zhang: Chinese PLA General Hospital
Yuanfeng Li: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Chengming Gao: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Hao Lu: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Xueting Wang: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Pengbo Cao: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Hongxia Chen: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine
Shichun Lu: Chinese PLA General Hospital
Gangqiao Zhou: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generate a single-cell atlas of the multicellular ecosystem of HCC from four tissue sites. We show the enrichment of central memory T cells (TCM) in the early tertiary lymphoid structures (E-TLSs) in HCC and assess the relationships between chronic HBV/HCV infection and T cell infiltration and exhaustion. We find the MMP9+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and PPARγ to be the pivotal transcription factor driving their differentiation. We also characterize the heterogeneous subpopulations of malignant hepatocytes and their multifaceted functions in shaping the immune microenvironment of HCC. Finally, we identify seven microenvironment-based subtypes that can predict prognosis of HCC patients. Collectively, this large-scale atlas deepens our understanding of the HCC microenvironment, which might facilitate the development of new immune therapy strategies for this malignancy.

Date: 2022
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DOI: 10.1038/s41467-022-32283-3

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