ArticleEBioMedicine2020
Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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48 citing papers in PubMed, 91 citations in OpenAlex.
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- Oncogenic function and transcriptional dynamics of MYCN in liver tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging for Predicting Immunotherapy Response in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.Liver cancer · 2026Review
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- ACVR2A attenuation impacts lactate production and hyperglycolytic conditions attracting regulatory T cells in hepatocellular carcinoma.Cell reports. Medicine · 2025Article
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- Profiling in advanced hepatocellular carcinoma: opening new doors for precision medicine.Hepatology international · 2025Article
- Radiofrequency ablation combined with immunotherapy to treat hepatocellular carcinoma: a comprehensive review.BMC surgery · 2025Review
- Development of mutated β-catenin gene signature to identifyJHEP reports : innovation in hepatology · 2024Article
- Development and validation of machine learning models for diagnosis and prognosis of lung adenocarcinoma, and immune infiltration analysis.Scientific reports · 2024Article
- FAM109B plays a tumorigenic role in low-grade gliomas and is associated with tumor-associated macrophages (TAMs).Journal of translational medicine · 2024Article
- Artificial ascites‑assisted microwave ablation for liver cancer adjacent to the diaphragm and perioperative nursing care.Oncology letters · 2024Article
- TREM1Journal of cancer research and clinical oncology · 2024Article
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- Immune cell dynamics and the impact on the efficiency of transvascular antitumor interventional therapies in hepatocellular carcinoma patients.Frontiers in immunology · 2024Observational
- Single-cell RNA sequencing in endometrial cancer: exploring the epithelial cells and the microenvironment landscape.Frontiers in immunology · 2024Review
- Lenvatinib activates anti-tumor immunity by suppressing immunoinhibitory infiltrates in the tumor microenvironment of advanced hepatocellular carcinoma.Communications medicine · 2023Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe tumor microenvironment can be classified into immunologically active "inflamed" tumors and inactive "non-inflamed" tumors based on the infiltration of cytotoxic immune cells. Previous studies on liver cancer have reported a superior prognosis for inflamed tumors compared to non-inflamed tumors. However, liver cancer is highly heterogeneous immunologically and genetically, and a finer classification of the liver cancer microenvironment may improve our understanding of its immunological diversity and response to immune therapy.
methodsWe characterized the immune gene signatures of 234 primary liver cancers, mainly virus-related, from a Japanese population using RNA-Seq of tumors and matched non-tumorous hepatitis livers. We then compared them with the somatic alterations detected using the whole-genome sequencing.
findingsLiver cancers expressed lower levels of immune marker genes than non-tumorous hepatitis livers, indicating immunosuppression in the tumor microenvironment. Several immunosuppression mechanisms functioned actively and mutually exclusively, resulting in four immune subclasses of liver cancer: tumor-associated macrophage (TAM), CTNNB1, cytolytic activity (CYT), and regulatory T cell (Treg). The CYT and Treg subclasses represented inflamed tumors, while the TAM and CTNNB1 subclasses represented non-inflamed tumors. The TAM subclass, which comprised 31% of liver cancers, showed a poor survival, expressed elevated levels of extracellular matrix genes, and was associated with somatic mutations of chromatin regulator ARID2. The results of cell line experiments suggested a functional link between ARID2 and chemokine production by liver cancer cells.
interpretationPrimary liver cancer was classified into four subclasses based on mutually exclusive mechanisms for immunosuppression. This classification indicate the importance of immunosuppression mechanisms, such as TAM and Treg, as therapeutic targets for liver cancer.
fundingThe Japan Agency for Medical Research and Development (AMED).
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