ArticleCancer immunology, immunotherapy : CII2020
Interferon regulatory factor 1 (IRF-1) and IRF-2 regulate PD-L1 expression in hepatocellular carcinoma (HCC) cells.
Article in Cancer immunology, immunotherapy : CII, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Pooled it
- SIRT7-Mediated H2BK120 Succinylation Drives Aberrant Mitophagy in Sepsis-Associated Cognitive Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tumor-Intrinsic DNA Damage Signaling Is Associated with MHC-I Expression and CD8 Cytotoxic T-Cell Engagement in Triple-Negative Breast Cancer.Current issues in molecular biology · 2026Article
- Current status and challenges of immune checkpoint inhibitors in liver cancer: from monotherapy to combination strategies.Medical oncology (Northwood, London, England) · 2026Review
- Impact of lymphocyte p-glycoprotein activity on development of graft-versus-host disease after stem cell transplantation.International journal of hematology · 2026Article
- Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.Cell reports. Medicine · 2026Article
- ANKRD49 promotes immune evasion in lung adenocarcinoma by activating the MEF2A/PD‑L1 axis.Biology direct · 2026Article
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Interferon Regulatory Factor 2 (IRF2) Suppression Enhances Murine Cardiac Allograft Survival Through Immune Evasion.Immunology · 2026Article
- Interferon Regulatory Factors in Alcohol-Associated Liver Disease: Cell-Type Programs, Danger Signaling, and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Uncovering cellular perturbations and key mediator communications in liver cancer using single-cell RNA sequencing.Frontiers in immunology · 2026Article
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Interferon in Liver Diseases: Recent Advances.Advances in therapy · 2025Review
- Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Reprogramming the tumor microenvironment: synergistic mechanisms of antibody-drug conjugates and immune checkpoint inhibitors.Antibody therapeutics · 2025Review
- A CLDN18.2-Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Interleukin-17A facilitates tumor progressionWorld journal of gastrointestinal oncology · 2025Article
- Uncovering selection pressures on the IRF gene family in bats' immune system.Immunogenetics · 2025Article
- The pivotal role of cytokines in liver disease pathogenesis and therapeutic potential.Frontiers in immunology · 2025Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The objective response rate of immune checkpoint blockade (ICB) in hepatocellular carcinoma (HCC) with anti PD-L1/PD-1 therapy is low. Discovering the signaling pathways regulating PD-L1 might help to improve ICB response rates. Here, we investigate transcription factors IRF-1 and IRF-2 signaling pathways regulating PD-L1 in HCC cells. In vivo studies show that IRF-1 and PD-L1 mRNA expression in human HCC tumors are significantly repressed compared with noncancerous background liver. IRF-1, IRF-2, and PD-L1 mRNA expression correlated positively in HCC tumors. Increased IRF-1 mRNA expression was observed in patients with well-differentiated or early stage HCC tumors. In vitro studies show that IFN-γ induces PD-L1 mRNA and protein expression through upregulation of IRF-1 in mouse and human HCC cells. IRF-1, IRF-2, and PD-L1 mRNA expression is upregulated in murine HCC by co-culture with effector T cells from spleen cells incubated with anti-CD3/CD28 antibodies. IRF-2 over-expression down-regulates IFN-γ induced PD-L1 promoter activity and protein levels in a dose-dependent manner. We identify two IRF-1 response elements (IRE1/IRE2) in the upstream 5'-flanking region of the CD274 (PD-L1) gene promoter. Site-directed mutagenesis shows both IRE1 and IRE2 are functional in transfection promoter assays. IRF-1 traditionally functions as tumor suppressor gene. However, these novel findings show a complex role for IRF-1 which upregulates PD-L1 in the inflammatory tumor microenvironment. IRF-1 antagonizes IRF-2 for binding to the IRE promoter element in PD-L1 which gives new insight to the regulation of PD-L1/PD-1 pathways in HCC ICB therapy.
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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.