Molecular Mechanisms of Immune Dysregulation in Triple-Negative Breast Cancer
| Author | Fatemeh Kianivala | en |
| Author | Negin Molazadeh | en |
| Author | Omar Layth Qassid | en |
| Orcid | Fatemeh Kianivala [0009-0008-1472-9421] | en |
| Orcid | Negin Molazadeh [0000-0003-2857-0649] | en |
| Orcid | Omar Layth Qassid [0000-0001-7745-1879] | en |
| Accessioned Date | 2026-11-09T14:11:24Z | |
| Issued Date | 2026-09-30 | en |
| Abstract | Context: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. The behavior of TNBC is strongly influenced by inflammatory and immunosuppressive mechanisms. The tumor microenvironment contains diverse immune, stromal, and vascular components that regulate tumor progression, metastasis, therapeutic response, and immune escape. Evidence Acquisition: The literature was identified by searching PubMed, Scopus, Web of Science, and clinical trial registries using the following keywords: triple-negative breast cancer, inflammation, immune dysregulation, tumor microenvironment, cytokines, and tumor-infiltrating lymphocytes. Priority was given to clinical trials, translational studies, systematic reviews, and mechanistic investigations published during the last decade; landmark earlier studies were also considered. Results: Inflammatory signaling represents a fundamental biological continuum in TNBC, spanning immune-desert, immune-excluded, and immune-inflamed phenotypes. Persistent activation of central inflammatory nodes, predominantly NF-κB and the reciprocal IL-6/JAK/STAT3 signaling axis, orchestrates cancer stemness, epithelial-mesenchymal transition, and immunosuppressive stromal remodeling. Clinically, landmark trials such as KEYNOTE-355 have demonstrated the benefit of combining pembrolizumab with chemotherapy in PD-L1-positive advanced disease with a combined positive score ≥ 10. However, reliance on a single biomarker, such as PD-L1 or tumor-infiltrating lymphocytes, remains inadequate to capture functional immune dysregulation. Conclusions: Chronic inflammation driven by crosstalk between NF-κB and IL-6/JAK/STAT3 sustains immunosuppression and therapeutic refractoriness in TNBC. Overcoming resistance will require moving beyond static biomarkers toward combination strategies that integrate checkpoint inhibitors with targeted inhibitors of these central inflammatory pathways. | en |
| DOI | https://doi.org/10.69107/jid-175174 | en |
| URI | https://brieflands.com/journals/jid/articles/175174 | en |
| Keyword | Triple-negative Breast Cancer | en |
| Keyword | Inflammation | en |
| Keyword | Tumor Microenvironment | en |
| Keyword | Immunotherapy | en |
| Publisher | Brieflands | en |
| Title | Molecular Mechanisms of Immune Dysregulation in Triple-Negative Breast Cancer | en |
| Type | Review Article | en |
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