Integrated Single Cell Analysis Reveals An Atlas of Tumor Associated Macrophages in Hepatocellular Carcinoma

Xinqiang Li; Ruixia Li; Xiaolong Miao; Xin Zhou; Bin Wu; Junning Cao; Chengyu Wang; Shipeng Li; Jinzhen Cai

doi:10.1007/s10753-024-02026-1

Integrated Single Cell Analysis Reveals An Atlas of Tumor Associated Macrophages in Hepatocellular Carcinoma

Inflammation. 2024 Apr 26. doi: 10.1007/s10753-024-02026-1. Online ahead of print.

Authors

Xinqiang Li^#^{1

2}, Ruixia Li^#³, Xiaolong Miao^{1

2}, Xin Zhou^{1

2}, Bin Wu^{1

2}, Junning Cao^{1

2}, Chengyu Wang^{1

2}, Shipeng Li⁴, Jinzhen Cai^{5

6}

Affiliations

¹ Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, China.
² Institute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, China.
³ Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ Department of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China. shipengli2010@163.com.
⁵ Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, China. caijinzhen@qdu.edu.cn.
⁶ Institute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, China. caijinzhen@qdu.edu.cn.

^# Contributed equally.

PMID: 38668836
DOI: 10.1007/s10753-024-02026-1

Abstract

Hepatocellular carcinoma (HCC), one of the most prevalent cancers globally, is closely associated with tumor-associated macrophages (TAMs), including monocyte-derived macrophages and liver-resident Kupffer cells. Understanding TAM heterogeneity at the cellular level is crucial for developing effective HCC prevention and treatment strategies. In this study, we conducted an integrated single-cell analysis of four cohorts (GSE140228, GSE125449, GSE149614 and GSE156625) to elucidate the TAM landscape in HCC. We identified 284 gene markers, termed Panmyeloid markers, that characterize myeloid cells within this context. Our analysis distinguished six clusters of monocyte-derived macrophages (Macro1-Macro6) and four clusters of Kupffer cells (Kupffer1-Kupffer4). Notably, CXCL10 + macrophages and MT1G + Kupffer cells, predominantly located within tumor tissues, exhibited distinct functional characteristics relevant to HCC. We also explored cellular communication between TAMs and T cells, uncovering potential signaling pathways such as the CXCL10/CXCL11-CXCR3 and CXCL12-CXCR4 networks. These findings enhance our understanding of TAMs in HCC and open new avenues for targeted therapeutic interventions.

Keywords: CXCL10 + Macrophages; Hepatocellular carcinoma; MT1G + Kupffer cells; Single-cell RNA sequencing; Tumor associated macrophages.

Abstract

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