ArticleMedComm2023
STAT4 facilitates PD-L1 level via IL-12R/JAK2/STAT3 axis and predicts immunotherapy response in breast cancer.
Article in MedComm, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 13 citations in OpenAlex.
- Identification of lncRNAs in Breast Cancer Through Bioinformatics Analysis: Implications for Pathogenesis and Prognostic Significance.Cancer medicine · 2026Article
- JAK/STAT-mediated regulation of PD-L1 expression in breast cancer: Molecular mechanisms and implications for immunotherapy.iScience · 2026Review
- FCGBP Promotes Glioma Growth by Regulating JAK2/STAT3/c-Myc Pathway.Cancer medicine · 2026Article
- Co-targeting ferroptosis and immune evasion through small molecules in breast cancer.Journal of translational internal medicine · 2025Article
- Article
- Immunotherapy in Triple-Negative Breast Cancer.Oncology and therapy · 2025Review
- Integrative multi-omics reveal NSUN2 facilitates glycolysis and histone lactylation-driven immune evasion in renal carcinoma.Genes and immunity · 2025Article
- The Differential Expression of the JAK/STAT Pathway in Breast Cancer Cells Transfected with Human Papillomavirus Oncogenes.Viruses · 2025Article
- Machine learning-based integration of DCE-MRI radiomics for STAT3 expression prediction and survival stratification in breast cancer.Frontiers in immunology · 2025Article
- NETs-related genes predict prognosis and are correlated with the immune microenvironment in osteosarcoma.Frontiers in oncology · 2025Article
- Grape seed proanthocyanidins improve lymphatic drainage and blood perfusion in secondary lymphedema models.Frontiers in oncology · 2025Article
- Signal Transducer and Activator of Transcription 4 (STAT4) Association with Pituitary Adenoma.Medicina (Kaunas, Lithuania) · 2024Article
- Transcription factor STAT4 counteracts radiotherapy resistance in breast carcinoma cells by activating the MALAT1/miR-21-5p/THRB regulatory network.American journal of cancer research · 2024Article
- STAT4 facilitates PD-L1 level via IL-12R/JAK2/STAT3 axis and predicts immunotherapy response in breast cancer.MedComm · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal transducer and activator of transcription 4 (STAT4) is a critical transcription factor for T helper cell differentiation and tumor cells. Although its prognostic role and gene function have been reported in several carcinomas, the role of STAT4 in vitro and in vivo in breast cancer remains poorly understood. The effect of STAT4 in immunotherapy is also unclear. Therefore, we integrated bulk transcriptomics, experiments, and single-cell transcriptomics to systematically analyze its function in prognosis and signaling pathway. Several clinical breast cancer cohorts confirmed STAT4 as a T-cell relevant prognostic biomarker. Overexpressed STAT4 increased programmed cell death ligand 1 (PD-L1) and major histocompatibility complex class II levels in breast cancer cells. In molecular mechanism, transcriptional synergy between STAT4 and STAT3 transactivated interleukin (IL)-12R and involved a positive feedback loop: STAT4/IL-12R/JAK2-STAT3-STAT4, which contributed to the upregulation of PD-L1 expression. The above signaling axis was defined as the STAT4-related pathway and its score was used to predict T-cell expansion and anti-PD1 treatment response. These findings highlight a novel molecular mechanism indirectly regulating PD-L1 through the STAT4-related pathway: IL-12R/JAK2-STAT3-STAT4/PD-L1, and it has potential application in predicting anti-PD-1 immunotherapy response, which may pave the way for stratified immunotherapy in breast cancer.
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