Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma.

Abstract

The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.

• Authors: Qiming Zhang, Yao He, Nan Luo, Shashank J Patel, Yanjie Han, Ranran Gao, Madhura Modak, Sebastian Carotta, Christian Haslinger, David Kind, Gregory W Peet, Guojie Zhong, Shuangjia Lu, Weihua Zhu, Yilei Mao, Mengmeng Xiao, Michael Bergmann, Xueda Hu, Sid P Kerkar, Anne B Vogt, Stefan Pflanz, Kang Liu, Jirun Peng, Xianwen Ren, Zemin Zhang
• Journal: Cell (Cell) Vol. 179 Issue 4 Pg. 829-845.e20 (Oct 31 2019) ISSN: 1097-4172 [Electronic] United States
• PMID: 31675496 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Cation Transport Proteins
• GPNMB protein, human
• LAMP3 protein, human
• Lysosomal Membrane Proteins
• Membrane Glycoproteins
• Neoplasm Proteins
• metal transporting protein 1
• Leukocyte Common Antigens

Topics

• Carcinoma, Hepatocellular (genetics, immunology, pathology)
• Cation Transport Proteins (genetics)
• Cell Communication (genetics, immunology)
• Cell Lineage (genetics, immunology)
• Dendritic Cells (immunology, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Inflammation (genetics, immunology, pathology)
• Leukocyte Common Antigens (immunology)
• Liver (immunology, pathology)
• Liver Neoplasms (genetics, immunology, pathology)
• Lymph Nodes (immunology, pathology)
• Lymphocytes (immunology, pathology)
• Lysosomal Membrane Proteins (genetics)
• Macrophages (immunology, pathology)
• Membrane Glycoproteins (genetics)
• Myeloid Cells (immunology, pathology)
• Neoplasm Proteins (genetics)
• Sequence Analysis, RNA
• Single-Cell Analysis
• Transcriptome (genetics, immunology)
• Tumor Microenvironment (genetics, immunology)