ArticleProceedings of the National Academy of Sciences of the United States of America2019
JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Malassezia restricta-Derived Extracellular Vesicles Drive Ovarian Cancer Progression Through JAK2/STAT3-Mediated M2 Macrophage Polarisation.Microbial biotechnology · 2026Article
- Extracellular vesicles from canine mammary tumor cells promote macrophage M2 polarization and enhance tumor progression.Veterinary research communications · 2026Article
- Sesquiterpenoids target IFIT family proteins and LIMK1: potential implications for the tumor microenvironment and macrophage infiltration.BMC cancer · 2026Article
- Role and Molecular Mechanisms of Aerobic Glycolysis in Gastrointestinal Tumors.Journal of Cancer · 2026Review
- Investigating the therapeutic mechanism of Bufei Decoction in COPD: Schisandrin B targets the TLR4/NF-κB/JAK-STAT signaling pathway.Hereditas · 2025Article
- Shaping Orthodontics of the Future: Concepts and Implications from a Cellular and Molecular Perspective.International journal of molecular sciences · 2025Review
- Low-dose radiotherapy enhances the efficacy of PD-L1 blockade and induces the abscopal effect.Journal for immunotherapy of cancer · 2025Article
- Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.Journal of translational medicine · 2025Review
- Mechanisms of Baicalin Alleviates Intestinal Inflammation: Role of M1 Macrophage Polarization and Lactobacillus amylovorus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tofacitinib downregulates JAK1 and JAK3 on human intestinal monocytes and macrophages without affecting dendritic cells phenotype or function.Journal of translational autoimmunity · 2025Article
- The role of macrophages in liver metastasis: mechanisms and therapeutic prospects.Frontiers in immunology · 2025Review
- Manipulating immune activity of macrophages: a materials and mechanics perspective.Trends in biotechnology · 2025Review
- Beyond CTLA-4 and PD-1: Novel Insights into MAO-A as a Next Generation Immune Checkpoint Modulator for Cancer Immunotherapy.Current cancer drug targets · 2025Review
- Macrophage Phenotypic Switch and Obesity-Associated Metabolic Risk: Mechanisms and Targets.Oxidative medicine and cellular longevity · 2025Review
- Review
- STAT signaling pathways in immune cells and their associated mechanisms in cancer pathogenesis.BioImpacts : BI · 2025Review
- Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer.Oncoimmunology · 2024Article
- C/EBPβ deletion in macrophages impairs mammary gland alveolar budding during the estrous cycle.Life science alliance · 2024Article
- DAB2IP inhibits glucose uptake by modulating HIF-1α ubiquitination under hypoxia in breast cancer.Oncogenesis · 2024Article
- Phosphorylation of FOXK2 at Thr13 and Ser30 by PDK2 sustains glycolysis through a positive feedback manner in ovarian cancer.Oncogene · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Tumor-associated macrophages contribute to tumor progression and therapeutic resistance in breast cancer. Within the tumor microenvironment, tumor-derived factors activate pathways that modulate macrophage function. Using in vitro and in vivo models, we find that tumor-derived factors induce activation of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in macrophages. We also demonstrate that loss of STAT3 in myeloid cells leads to enhanced mammary tumorigenesis. Further studies show that macrophages contribute to resistance of mammary tumors to the JAK/STAT inhibitor ruxolitinib in vivo and that ruxolitinib-treated macrophages produce soluble factors that promote resistance of tumor cells to JAK inhibition in vitro. Finally, we demonstrate that STAT3 deletion and JAK/STAT inhibition in macrophages increases expression of the protumorigenic factor cyclooxygenase-2 (COX-2), and that COX-2 inhibition enhances responsiveness of tumors to ruxolitinib. These findings define a mechanism through which macrophages promote therapeutic resistance and highlight the importance of understanding the impact of targeted therapies on the tumor microenvironment.
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