IRF1
IRF1
Overview
IRF1, or interferon regulatory factor 1, is a transcription factor that plays a central role in immune and inflammatory gene regulation. It is best known for mediating interferon-responsive transcriptional programs and for integrating signals from pathways such as JAK2/STAT3 signaling, MAPK signaling, and mechanistic target of rapamycin kinase-related networks. In cancer and inflammatory biology, IRF1 is often studied as a context-dependent regulator of cell-state transitions, cytokine responses, and immune checkpoint-related pathways.
Recent studies have highlighted IRF1 as a biologically important node linking pathway inhibition to downstream transcriptional reprogramming. Depending on the cellular context, IRF1 can promote proinflammatory responses, regulate genes involved in immune evasion or antitumor immunity, and participate in transcriptional complexes that influence tumor progression and therapy response. Its relevance spans endothelial inflammation, cholangiocarcinoma, non-small cell lung cancer, and KRAS-MAPK-driven adaptive signaling.
Recent Publications Focus
Below is a summary of the newest research publications targeting IRF1 (sorted by publication date).
Recent studies have identified IRF1 as a central transcriptional regulator bridging tumor immunogenicity and immune checkpoint therapy responses across multiple cancer types. In urothelial carcinoma, PIK3CA mutations enhanced tumor immunogenicity through activation of the IRF1-NLRC5-MHC-I axis, promoting antigen presentation and CD8+ T-cell-mediated cytotoxicity in response to anti-PD-L1 therapy [42413983]. In non-small cell lung cancer, the IRF1-TRIM21 axis enhanced anti-tumor immunity by promoting proteasomal degradation of the immune checkpoint ligand FGL1, with artemisinin shown to upregulate this pathway and sensitize tumors to anti-PD-1 immunotherapy [42020516]. These findings extend to metabolic intervention, where metformin suppressed PD-L1 expression through SLC5A11-mediated AMPK-IRF1 signaling, synergizing with checkpoint inhibitors to enhance anti-tumor T-cell responses in syngeneic cancer models [41690450].
IRF1 also functions as a critical hub in inflammatory responses triggered by kinase inhibition and programmed cell death pathways. Mammalian target of rapamycin (mTOR) inhibition upregulated IRF1 in endothelial cells, linking it to myosin light chain kinase-dependent cytoskeletal contraction and proinflammatory cytokine expression, which collectively promoted endothelial hyperpermeability and pulmonary inflammation [42273992]. In pancreatic ductal adenocarcinoma, prolonged Kras-MAPK inhibition induced IRF1 and IRF9-driven interferon signaling that activated TRIM22 and downstream NF-κB signaling, ultimately promoting epithelial-to-mesenchymal transition and therapeutic resistance [42008116]. Additionally, IRF1 emerged as a core regulator of PANoptosis—an integrated programmed cell death mechanism incorporating pyroptosis, apoptosis, and necroptosis—in lung adenocarcinoma, where it coordinated death and inflammation-related pathways and served as a target for immune-enhancing interventions such as ginsenosides [41935997].
Transcriptional regulation of IRF1 target genes further demonstrates its role in controlling tumor progression and immune suppression. In large-duct type intrahepatic cholangiocarcinoma, IRF1 forms a transcriptional complex with OGT to control MUC16 expression; disruption of this complex by the small-molecule inhibitor OSMI-1 suppressed MUC16-mediated tumor growth and synergized with gemcitabine [41839437]. Collectively, these studies establish IRF1 as a multifunctional regulator controlling antigen presentation, immune checkpoint expression, inflammatory responses, and cell state transitions, positioning it as an attractive therapeutic target for modulation through pharmacological agents or combination with immunotherapies.