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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1446453
This article is part of the Research Topic Single-Cell Sequencing of the Immune Microenvironment in Cancer View all 4 articles
Identification of SPP1+ macrophages as an immune suppressor in hepatocellular carcinoma using single-cell and bulk transcriptomics
Provisionally accepted
Han Jin
1,2,3*
Woonghee Kim
2,3
Meng Yuan
2,3
Xiangyu Li
2,3
Hong Yang
2,3
Mengzhen Li
2,3
Mengnan Shi
2,3
HASAN TURKEZ
4
Mathias Uhlen
2,3
Cheng Zhang
2,3
Adil Mardinoglu
2,3,5*- 1 Central Laboratory, Tianjin Medical University General Hospital, Tianjin, China
- 2 Science for Life Laboratory (SciLifeLab), Solna, Sweden
- 3 Royal Institute of Technology, Stockholm, Stockholm, Sweden
- 4 Department of Medical Biology, Atatürk University, Erzurum, Erzurum, Türkiye
- 5 King's College London, London, England, United Kingdom
Macrophages and T cells play crucial roles in liver physiology, but their functional diversity in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we analyzed RNA-sequencing (RNA-seq) data from two large-scale HCC cohorts, revealing a major and consensus gene co-expression cluster with significant implications for immunosuppression. Notably, these genes exhibited higher enrichment in liver macrophages than T cells, as confirmed by single-cell RNA-sequencing (scRNA-seq) data from HCC patients. Integrative analysis of bulk and single-cell RNA-seq data pinpointed SPP1+ macrophages as an unfavorable cell type, while VCAN+ macrophages, C1QA+ macrophages, and CD8+ T cells were associated with a more favorable prognosis for HCC patients. Subsequent scRNA-seq investigations and in vitro experiments elucidated that SPP1, predominantly secreted by SPP1+ macrophages, inhibits CD8+ T cell proliferation. Finally, targeting SPP1 in tumor-associated macrophages through inhibition led to a shift towards a favorable phenotype. In conclusion, this study underpins the potential of SPP1 as a translational target in immunotherapy for HCC.
Keywords: Hepatocellular Carcinoma, co-expression network, tumor-associated macrophage, Macrophage heterogeneity, single-cell sequencing
Received: 09 Jun 2024; Accepted: 19 Nov 2024.
Copyright: © 2024 Jin, Kim, Yuan, Li, Yang, Li, Shi, TURKEZ, Uhlen, Zhang and Mardinoglu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Han Jin, Central Laboratory, Tianjin Medical University General Hospital, Tianjin, 300052, China
Adil Mardinoglu, Science for Life Laboratory (SciLifeLab), Solna, Sweden
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