ArticleBritish journal of pharmacology2021
STAT3/NF-κB signalling disruption in M2 tumour-associated macrophages is a major target of PLGA nanocarriers/PD-L1 antibody immunomodulatory therapy in breast cancer.
Article in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Macrophage Membrane-Engineered Biomimetic Nanoplatform Enables Immune Evasion and Immunomodulation for Enhanced Chemo-Photodynamic Therapy.Biomacromolecules · 2026Article
- Creatine monohydrate modulates testicular morphology and SOD1/NFκB-p65 immunoexpression in streptozotocin-induced diabetic rats.Journal of molecular histology · 2026Article
- JAK/STAT-mediated regulation of PD-L1 expression in breast cancer: Molecular mechanisms and implications for immunotherapy.iScience · 2026Review
- Harnessing nanomedicine to target NF-κB signalling in cancer: at the intersection of inflammatory signalling, metabolic reprogramming, and therapeutic innovation.Cell communication and signaling : CCS · 2026Review
- The puppet master in the breast cancer "microecological community": spatial and metabolic regulation of macrophage heterogeneity.Molecular cancer · 2026Review
- PEAK1 promotes prostate cancer progression and docetaxel resistance by mediating the polarization of tumor-associated macrophages.European journal of medical research · 2026Article
- Preclinical Nanoparticle Approaches Targeting Tumor-Associated Macrophages in Breast Cancer: From Mechanisms to Therapeutic Strategies.International journal of nanomedicine · 2026Review
- Hybrid System of Magnetic Nanoparticles and Cashew-Gum Nanoparticles Induce Apoptosis and Tumor Necrosis in Colorectal Cancer.ACS omega · 2025Article
- FOXP3 Polymorphism and Upregulation of the CXCL12-CXCR4-SNAIL Axis with High Infiltration of M2TAM by STAT3/NFKB Pathways Influence the Survival of Cervical Cancer Patients.Advanced biology · 2025Article
- M1 Macrophage Extracellular Vesicles and TLR3 Agonist Nanoparticles Down-Regulate Immunosuppression and Metastasis via AKT/TAM in Triple-Negative Breast Cancer.Molecular carcinogenesis · 2025Article
- Elevated tumor NOS2/COX2 promotes immunosuppressive phenotypes associated with poor survival in ER- breast cancer.JCI insight · 2025Article
- Targeting breast tumor extracellular matrix and stroma utilizing nanoparticles.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Article
- [Dihydroartemisinin enhances doxorubicin-induced apoptosis of triple negative breast cancer cells by negatively regulating the STAT3/HIF-1α pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumor-associated macrophages within the immunological milieu: An emerging focal point for therapeutic intervention.Heliyon · 2024Review
- Enhancing cancer immunotherapy: Nanotechnology-mediated immunotherapy overcoming immunosuppression.Acta pharmaceutica Sinica. B · 2024Review
- Article
- Understanding Gene Involvement in Hepatocellular Carcinoma: Implications for Gene Therapy and Personalized Medicine.Pharmacogenomics and personalized medicine · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeInflammation associated with the tumour microenvironment (TME) is critical for cancer development, and immunotherapeutic strategies modulating the immune response in cancer have been crucial. In this study, a methotrexate-loaded (MTX) poly(lactic-co-glycolic acid)-based (PLGA) drug nanocarrier covered with polyethyleneimine (Pei) and hyaluronic acid (HA) was developed and combined with an PD-L1 antibody to investigate anti-cancer and immunomodulatory effects in breast cancer TME. EXPERIMENTAL APPROACH: Naked or HA-coated PeiPLGA-MTX nanoparticles (NPs) were assessed on 4T1 breast cancer cells grown in culture and in a mouse model of orthotopic tumour growth. Tumours were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and cell migration were analysed in vitro in 4T1 cells. Polarization of murine macrophages (RAW cells) was also carried out. KEY
resultsNaked or HA-coated PeiPLGA-MTX NPs used alone or combined with PD-L1 antibody modified the tumourigenic course by TME immunomodulation, leading to reduction of primary tumour size and metastases. STAT3 and NF-κB were the major genes downregulated by NPs. In tumor-associated macrophages (TAM) such regulation switched M2 phenotype (CD163) towards M1 (CD68) and reduced levels of IL-10, TGF-β and CCL22. Moreover, malignant cells showed overexpression of FADD, APAF-1, caspase-3 and E-cadherin, and decreased expression of Bcl-2, MDR-1, survivin, vimentin, CXCR4 and PD-L1 after treatment with NPs. CONCLUSION AND IMPLICATIONS: NPs-mediated STAT3/NF-κB signalling axis suppression disrupted crosstalk between immune and malignant cells, reducing immunosuppression and critical pro-tumour events. These findings provide a promising therapeutic approach capable of guiding the immune TME to suppress the development of breast cancer.
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