ArticleOncoimmunology
IL-6 augments IL-4-induced polarization of primary human macrophages through synergy of STAT3, STAT6 and BATF transcription factors.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- The monoacylglycerol acyltransferase 2 inhibitor VB-85387 reduces MASLD.Journal of lipid research · 2026Article
- Inhibiting CXCL12/CXCR4 axis enhances T cell activity in gastric cancer.Cancer gene therapy · 2026Article
- Hepatic Stellate Cell-derived IL-11 Exacerbates Liver Fibrosis via Interplay between HSCs and Macrophages.International journal of biological sciences · 2026Article
- PRKCSH deficiency promotes an anti-tumor immune microenvironment via UPR activation and M1 macrophage polarization.Cancer cell international · 2025Article
- Advances in Tumor-Derived Exosomal Non-Coding RNAs Regulating M2 Macrophage Polarization: Molecular Mechanisms and Signaling Pathway.Cancer medicine · 2025Review
- FPR1-dependent Pro-inflammatory Ccl4Respiratory research · 2025Article
- Co-targeting JAK1/STAT6/GAS6/TAM signaling improves chemotherapy efficacy in Ewing sarcoma.Nature communications · 2024Article
- Interleukin-6: An Under-Appreciated Inducer of Thermogenic Adipocyte Differentiation.International journal of molecular sciences · 2024Review
- The role of tumor-associated macrophages in hepatocellular carcinoma progression: A narrative review.Cancer medicine · 2023Review
- Double-edged sword of JAK/STAT signaling pathway in viral infections: novel insights into virotherapy.Cell communication and signaling : CCS · 2023Review
- A Rare Case of Orbital Castleman Disease with Overlapping IgG4-Related Disease.Medicina (Kaunas, Lithuania) · 2023Article
- Ang-(1-7)/MasR axis promotes functional recovery after spinal cord injury by regulating microglia/macrophage polarization.Cell & bioscience · 2023Article
- IL-6/ERK signaling pathway participates in type I IFN-programmed, unconventional M2-like macrophage polarization.Scientific reports · 2023Article
- Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling.Inflammation and regeneration · 2023Article
- Circular RNA circWWC3 augments breast cancer progression through promoting M2 macrophage polarization and tumor immune escape via regulating the expression and secretion of IL-4.Cancer cell international · 2022Article
- Roles for macrophage-polarizing interleukins in cancer immunity and immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- The Mechanism and Regulation of the NLRP3 Inflammasome during Fibrosis.Biomolecules · 2022Review
- Systematic Construction and Validation of a Novel Macrophage Differentiation-Associated Prognostic Model for Clear Cell Renal Cell Carcinoma.Frontiers in genetics · 2022Article
- Analysis framework and experimental design for evaluating synergy-driving gene expression.Nature protocols · 2021Article
- Angelicin Alleviates Post-Trauma Osteoarthritis Progression by Regulating Macrophage Polarization via STAT3 Signaling Pathway.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages in the tumor microenvironment respond to complex cytokine signals. How these responses shape the phenotype of tumor-associated macrophages (TAMs) is incompletely understood. Here we explored how cytokines of the tumor milieu, interleukin (IL)-6 and IL-4, interact to influence target gene expression in primary human monocyte-derived macrophages (hMDMs). We show that dual stimulation with IL-4 and IL-6 synergistically modified gene expression. Among the synergistically induced genes are several targets with known pro-tumorigenic properties, such as CC-chemokine ligand 18 (CCL18), transforming growth factor alpha (TGFA) or CD274 (programmed cell death 1 ligand 1 (PD-L1)). We found that transcription factors of the signal transducer and activator of transcription (STAT) family, STAT3 and STAT6 bind regulatory regions of synergistically induced genes in close vicinity. STAT3 and STAT6 co-binding further induces the basic leucine zipper ATF-like transcription factor (BATF), which participates in synergistic induction of target gene expression. Functional analyses revealed increased MCF-7 and MDA-MB 231 tumor cell motility in response to conditioned media from co-treated hMDMs compared to cells incubated with media from single cytokine-treated hMDMs. Flow cytometric analysis of T cell populations upon co-culture with hMDMs polarized by different cytokines indicated that dual stimulation promoted immunosuppressive properties of hMDMs in a PD-L1-dependent manner. Analysis of clinical data revealed increased expression of BATF together with TAM markers in tumor stroma of breast cancer patients as compared to normal breast tissue stroma. Collectively, our findings suggest that IL-4 and IL-6 cooperate to alter the human macrophage transcriptome, endowing hMDMs with pro-tumorigenic properties.
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