ArticleInflammation2022
Interferon Gamma-Induced Interferon Regulatory Factor 1 Activates Transcription of HHLA2 and Induces Immune Escape of Hepatocellular Carcinoma Cells.
Article in Inflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Breakthroughs in HBV-related HCC Therapy: The Unmatched Potential of Immune Checkpoint Inhibitors.Current treatment options in oncology · 2026Review
- Crosstalk between tumor-associated macrophages and the B7/CD28 family in immune checkpoint inhibitor-induced immunotherapy.Molecular and cellular biochemistry · 2026Review
- Combination Therapy Approaches to Enhance the Efficacy of ERV-Targeting Vaccines in Cancer.Cancer immunology research · 2025Review
- Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.Frontiers in oncology · 2025Review
- HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer.Endocrine oncology (Bristol, England) · 2025Review
- B7-H7 knockdown suppresses the proliferation, metastasis, and drug resistance of B-cell non-Hodgkin lymphoma cells by inhibiting the PI3K/Akt pathway.Frontiers in oncology · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Unlocking the potential of HHLA2: identifying functional immune infiltrating cells in the tumor microenvironment and predicting clinical outcomes in laryngeal squamous cell carcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- Deciphering fatty acid biosynthesis-driven molecular subtypes in pancreatic ductal adenocarcinoma with prognostic insights.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- LINC00665 promotes the progression and immune evasion of lung cancer by facilitating the translation of TCF7 protein through dependence on IRES.Cancer cell international · 2024Article
- The Role of Interferon Regulatory Factors in Liver Diseases.International journal of molecular sciences · 2024Review
- Key role of interferon regulatory factor 1 (IRF-1) in regulating liver disease: progress and outlook.Journal of Zhejiang University. Science. B · 2024Review
- In vitro Immunostimulant Activity of the Polyphenolic Extract from the Arctic Brown Algae Fucus vesiculosus.Plant foods for human nutrition (Dordrecht, Netherlands) · 2024Article
- Review
- The role of tumor-associated macrophages in hepatocellular carcinoma progression: A narrative review.Cancer medicine · 2023Review
- Regulation of HHLA2 expression in kidney cancer and myeloid cells.BMC cancer · 2023Article
- CancerHERVdb: Human Endogenous Retrovirus (HERV) Expression Database for Human Cancer Accelerates Studies of the Retrovirome and Predictions for HERV-Based Therapies.Journal of virology · 2023Article
- A new prediction model of hepatocellular carcinoma based on N7-methylguanosine modification.BMC gastroenterology · 2023Article
- Tumor-secreted lactate contributes to an immunosuppressive microenvironment and affects CD8 T-cell infiltration in glioblastoma.Frontiers in immunology · 2023Article
- Human endogenous retrovirus-H long terminal repeat-associating 2: The next immune checkpoint for antitumour therapy.EBioMedicine · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Immunosuppression developed by cancer cells remains a leading cause of treating failure of immunotherapies. This study aimed to explore the function of human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), an immune checkpoint molecule from the B7 family, in the immune escape in hepatocellular carcinoma (HCC). Mouse models with primary HCC or with xenograft tumors were established. The portion of tumor-associated macrophages (TAMs) and the level of PD-L1 in the tumor tissues were examined. THP-1 cells were treated with PMA to obtain a macrophage-like phenotype. The PMA-treated THP-1 cells were co-cultured with the HCC cells in Transwell chambers to examine the function of HHLA2 in chemotactic migration and polarization of macrophages. HHLA2 expression was correlated with infiltration of immune cells, especially macrophages, and was linked to poor prognosis of patients with HCC. HHLA2 knockdown reduced incidence rate of primary HCC in mice. It also reduced tumor metastasis, the portion of M2 macrophages, and the expression of PD-L1 in primary and xenograft tumors. In vitro, HHLA2 upregulation increased expression of PD-L1 in HCC cells indirectly by inducing M2 polarization and chemotactic migration of macrophages. Interferon gamma (IFNG) enhanced expression of interferon regulatory factor 1 (IFR1) in HCC cells, and IFR1 bound to the promoter region of HHLA2 to activate HHLA2 expression. This study suggested that the IFNG/IFR1/HHLA2 axis in HCC induces M2 polarization and chemotactic migration of macrophages, which leads to immune escape and development of HCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.