ArticleBreast cancer research : BCR2015
Human breast cancer cells educate macrophages toward the M2 activation status.
Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers, 1 of them a synthesis that pooled it.
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Who cites it
252 citing papers in PubMed, 1 synthesis or guideline pooled it, 420 citations in OpenAlex.
- The Prognostic and Clinical Value of Tumor-Associated Macrophages in Patients With Breast Cancer: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2022Pooled it
- Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026Article
- SLAMF8 promotes tumor growth of gastric cancer by enhancing M2 polarization of tumor-associated macrophages.Journal of translational medicine · 2026Article
- Breast Cancer Milieu Maneuvers Cancer-Associated Macrophages to Synergize Neoplastic Repertoires.Cancers · 2026Review
- Article
- Characterization of Oncogenic and Immunogenic Profiling in Patients with Breast Cancer Tumors After Radiation Therapy.International journal of molecular sciences · 2026Article
- MLK4 orchestrates macrophage-induced triple-negative breast cancer invasion and ECM remodeling via enhanced paracrine signaling and NF-κB-MMP axis activation.Cell death & disease · 2026Article
- Virus-based IFNγ gene delivery and photodynamic therapy cooperate to remodel the tumor microenvironment and suppress breast cancer.Molecular therapy. Oncology · 2026Article
- Necroptosis in both tumour and stromal compartments determines responsiveness to immunogenic cell death-based immunotherapy.Nature communications · 2026Article
- Lutein reverses M2 macrophages polarization and exhibits antitumor effects on human triple-negative breast cancer cells.Molecular biology reports · 2026Article
- CD155 Expression in Invasive Breast Carcinoma: Association with Immune Tumor Microenvironment.Iranian journal of pathology · 2026Article
- Chemical Surface Modification Tolerance of Primary and Immortalized Macrophages and Stem Cells.Chembiochem : a European journal of chemical biology · 2025Article
- Secreted frizzled-related protein 2 monoclonal antibody-mediated IFN-ϒ reprograms tumor-associated macrophages to suppress triple negative breast cancer.Breast cancer research : BCR · 2025Article
- Pericytes orchestrate a tumor-restraining microenvironment in glioblastoma.Nature communications · 2025Article
- Empowering chemotherapy-induced antitumor immunity by multi-targeted synergistic combination nanomedicine for triple-negative breast cancer.Materials today. Bio · 2025Article
- Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value-A Review.Veterinary sciences · 2025Review
- Interaction Between Mesenchymal Stromal Cells and Tumor Cells Present in Cervical Cancer Influences Macrophage Polarization.Cancers · 2025Article
- Article
- Decoding tumor-infiltrating lymphocytes heterogeneity in ductal carcinoma in situ: immune microenvironment dynamics and prognostic insights.Discover oncology · 2025Review
- Roles of Peripheral Nerves in Tumor Initiation and Progression.International journal of molecular sciences · 2025Review
192 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe immune system plays a major role in cancer progression. In solid tumors, 5-40 % of the tumor mass consists of tumor-associated macrophages (TAMs) and there is usually a correlation between the number of TAMs and poor prognosis, depending on the tumor type. TAMs usually resemble M2 macrophages. Unlike M1-macrophages which have pro-inflammatory and anti-cancer functions, M2-macrophages are immunosuppressive, contribute to the matrix-remodeling, and hence favor tumor growth. The role of TAMs is not fully understood in breast cancer progression.
methodsMacrophage infiltration (CD68) and activation status (HLA-DRIIα, CD163) were evaluated in a large cohort of human primary breast tumors (562 tissue microarray samples), by immunohistochemistry and scored by automated image analysis algorithms. Survival between groups was compared using the Kaplan-Meier life-table method and a Cox multivariate proportional hazards model. Macrophage education by breast cancer cells was assessed by ex vivo differentiation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of breast cancer cell conditioned media (MDA-MB231, MCF-7 or T47D cell lines) and M1 or M2 inducing cytokines (respectively IFN-γ, IL-4 and IL-10). Obtained macrophages were analyzed by flow cytometry (CD14, CD16, CD64, CD86, CD200R and CD163), ELISA (IL-6, IL-8, IL-10, monocyte colony stimulating factor M-CSF) and zymography (matrix metalloproteinase 9, MMP-9).
resultsClinically, we found that high numbers of CD163(+) M2-macrophages were strongly associated with fast proliferation, poor differentiation, estrogen receptor negativity and histological ductal type (p<0.001) in the studied cohort of human primary breast tumors. We demonstrated ex vivo that breast cancer cell-secreted factors modulate macrophage differentiation toward the M2 phenotype. Furthermore, the more aggressive mesenchymal-like cell line MDA-MB231, which secretes high levels of M-CSF, skews macrophages toward the more immunosuppressive M2c subtype.
conclusionsThis study demonstrates that human breast cancer cells influence macrophage differentiation and that TAM differentiation status correlates with recurrence free survival, thus further emphasizing that TAMs can similarly affect therapy efficacy and patient outcome.
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