Background: Immunotherapy is revolutionizing the management of advanced non-small cell lung cancer (NSCLC). However, sustained responses are observed in only a minority of patients. Reliable biomarkers are required to identify potential beneficiaries. Interferon regulatory factor 4 (IRF4) plays a crucial role in immune regulation, suggesting its potential as a prognostic biomarker in NSCLC immunotherapy. This study aimed to investigate the predictive role of IRF4 expression in patients with NSCLC receiving immunotherapy.
Methods: Data from three NSCLC cohorts treated with immune checkpoint inhibitors were collected from the Gene Expression Omnibus (GEO) database. The prognostic significance of IRF4 was assessed across these cohorts, and gene set enrichment analysis (GSEA) was performed. IRF4-based nomograms were developed to predict the outcomes of immunotherapy. Correlations among IRF4 expression, immune cell infiltration, and immunotherapy prognosis were evaluated in our cohort.
Results: Elevated IRF4 expression was associated with improved prognosis in patients with NSCLC undergoing immunotherapy, consistent with both GEO dataset and our cohort. IRF4 emerged as an independent predictor for progression-free survival (PFS) and overall survival (OS) in multivariable Cox regression analysis. GSEA analysis highlighted links between IRF4 expression and immune activation pathways such as Chemokine_Signaling_Pathway, Natural_Killer_Cell_Mediated_Cytotoxicity, B_Cell_Receptor_Signaling_Pathway, and T_Cell_Receptor_Signaling_Pathway. In our cohort, immunohistochemistry demonstrated correlations between IRF4 expression and the infiltration of CD8+ T cells, CD20+ B cells, and PD-L1 expression in the tumor microenvironment.
Conclusion: High IRF4 expression in baseline tumor tissue could serve as a favorable predictor of NSCLC immunotherapy outcomes, aiding in personalized treatment strategies.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.intimp.2024.113411 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Utilising bioinformatics and systems biology methods to uncover the impact of dermatomyositis on interstitial lung disease.
Clin Exp Rheumatol
January 2025
Department of Oncology and Vascular Interventional Radiology, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Objectives: Dermatomyositis (DM) is frequently associated with interstitial lung disease (ILD); however, the molecular mechanisms underlying this association remain unclear. This study aimed to employ bioinformatics approaches to identify potential molecular mechanisms linking DM and ILD.
Methods: GSE46239 and GSE47162 were analysed to identify common differentially expressed genes (DEGs).
Effects of dioscin from Dioscorea nipponica on TL1A/DR3 and Th9 cells in a collagen-induced arthritis mouse model.
Int Immunopharmacol
January 2025
Department of Anatomy, Basic Medical Institute, Chengde Medical University, Chengde 067000 Hebei, China. Electronic address:
Rheumatoid arthritis (RA) is a systemic autoimmune disease, and TL1A and its receptor DR3 play important roles in its pathogenesis. Th9 cells are involved in RA development. Dioscin from Dioscorea nipponica (DDN) has a therapeutic effect on RA, but its effect on TL1A/DR3 and Th9 cells remains unclear.
View Article and Find Full Text PDFDesign, synthesis and biological evaluation of bisnoralcohol derivatives as novel IRF4 inhibitors for the treatment of multiple myeloma.
Eur J Med Chem
January 2025
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China. Electronic address:
Interferon regulatory factor 4 (IRF4) is specifically overexpressed in multiple myeloma (MM) and mediates MM progression and survival, making it an emerging target for MM treatment. However, no chemical entity with a defined structure capable of directly binding to and inhibiting IRF4 has been reported. We screened our small library of steroid analogs and identified bisnoralcohol (BA) derivative 18 as a novel hit compound capable of inhibiting IRF4, with an IC of 13.
View Article and Find Full Text PDFUncovering selection pressures on the IRF gene family in bats' immune system.
Immunogenetics
January 2025
Laboratorio de Bioconservación y Manejo, Posgrado en Ciencias Químicobiológicas, Departamento de Zoología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación Carpio y Plan de Ayala S/N, Col. Santo Tomás, C.P. 11340, Ciudad de México, Mexico.
Unlike other mammals, bats serve as natural reservoirs for several highly pathogenic viruses without exhibiting symptoms of infection. Recent research has explored the complex mechanisms underlying the balance between bats' antiviral defenses and their pathological responses. However, the evolution of the molecular drivers behind bats' antiviral strategies remains largely unknown.
View Article and Find Full Text PDFEscape of Kdm6a from X Chromosome Is Detrimental to Ischemic Brains via IRF5 Signaling.
Transl Stroke Res
January 2025
Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our previous study has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!