Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients

Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-CD86low/-CD80low/-CD163low/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.

• Publication year

  2015

• Venue

  PLoS ONE

• Publication date

  2015-05-20

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0127028PMID 25992611PMCID 4439153
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Alarmins MRP8 and MRP14 induce stress tolerance in phagocytes under sterile inflammatory conditions.

  2014cited by this paper
• A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram‐positive cases

  2014cited by this paper
• Parallels between cancer and infectious disease.

  2014cited by this paper
• Immunosuppressive CD14+HLA-DRlow/neg IDO+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation

  2013cited by this paper
• Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets

  2013cited by this paper
• Monocytes mediate metastatic breast tumor cell adhesion to endothelium under flow

  2013cited by this paper
• Endogenous HMGB1 is required in endotoxin tolerance.

  2013cited by this paper
• Gene expression profiling reveals the defining features of monocytes from septic patients with compensatory anti-inflammatory response syndrome.

  2012influential reference
• S100A9 a new marker for monocytic human myeloid‐derived suppressor cells

  2012cited by this paper
• T-regulatory cells: key players in tumor immune escape and angiogenesis.

  2012cited by this paper
• Myeloid Cells Obtained from the Blood but Not from the Tumor Can Suppress T-cell Proliferation in Patients with Melanoma

  2012cited by this paper
• Wnt5a Induces a Tolerogenic Phenotype of Macrophages in Sepsis and Breast Cancer Patients

  2012cited by this paper
• On the armament and appearances of human myeloid-derived suppressor cells.

  2012influential reference
• The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

  2012cited by this paper
• Coordinated regulation of myeloid cells by tumours

  2012cited by this paper
• Increased Circulating Immunosuppressive CD14+HLA-DR−/Low Cells Correlate with Clinical Cancer Stage and Pathological Grade in Patients with Bladder Carcinoma

  2011cited by this paper
• A Paradoxical Role for Myeloid-Derived Suppressor Cells in Sepsis and Trauma

  2011cited by this paper
• A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells.

  2011cited by this paper
• Endotoxin Tolerance Represents a Distinctive State of Alternative Polarization (M2) in Human Mononuclear Cells

  2011cited by this paper
• Systemic immune suppression in glioblastoma: the interplay between CD14+HLA-DRlo/neg monocytes, tumor factors, and dexamethasone.

  2010cited by this paper
• Nomenclature of monocytes and dendritic cells in blood.

  2010cited by this paper
• Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign.

  2010cited by this paper
• Immunosuppressive CD14+HLA‐DRlow/− monocytes in prostate cancer

  2010influential reference
• Gene expression profiling of peripheral blood cells for early detection of breast cancer

  2010cited by this paper
• BASE - 2nd generation software for microarray data management and analysis

  2009influential reference
• Endotoxin tolerance: new mechanisms, molecules and clinical significance.

  2009influential reference
• Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor κB

  2009cited by this paper
• Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance

  2008cited by this paper
• Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy

  2008cited by this paper
• A genome-wide analysis of LPS tolerance in macrophages.

  2008cited by this paper
• Human monocytes augment invasiveness and proteolytic activity of inflammatory breast cancer

  2008cited by this paper
• Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

  2008cited by this paper
• Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

  2008cited by this paper
• CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells

  2006cited by this paper
• Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.

  2006cited by this paper
• Immune suppression in cancer: effects on immune cells, mechanisms and future therapeutic intervention.

  2006cited by this paper
• Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse.

  2006cited by this paper
• Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

  2005cited by this paper
• Filter Buffy Coats (FBC): a source of peripheral blood leukocytes recovered from leukocyte depletion filters.

  2005cited by this paper
• Modulation of monocyte matrix metalloproteinase-2 by breast adenocarcinoma cells

  2005cited by this paper
• From the Cover: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

  2005cited by this paper
• Dendritic Cell Infiltration and Prognosis of Early Stage Breast Cancer

  2004cited by this paper
• Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival

  2004cited by this paper
• Analysis of dendritic cells in tumor-free and tumor-containing sentinel lymph nodes from patients with breast cancer

  2004cited by this paper
• The three Es of cancer immunoediting.

  2004cited by this paper
• Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

  2003cited by this paper
• TM4: a free, open-source system for microarray data management and analysis.

  2003cited by this paper
• Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes.

  2002cited by this paper
• Cancer immunoediting: from immunosurveillance to tumor escape

  2002cited by this paper
• Immature myeloid cells and cancer-associated immune suppression

  2002cited by this paper
• Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes

  2002cited by this paper
• Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro‐ and antiinflammatory stimuli

  2000cited by this paper
• Errata

  1996cited by this paper
• Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma.

  1996cited by this paper
• Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells

  1996cited by this paper
• The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients.

  1993cited by this paper
• The novel subset of CD14+/CD16+ blood monocytes exhibits features of tissue macrophages

  1993cited by this paper
• Cáncer

  1939cited by this paper

• Distinct Roles of Monocyte Subsets in Cancer

  2025cites this paper
• Combined elevation of myeloid-derived suppressor cells and Tregs predicts lymph node metastasis in breast cancer

  2025cites this paper
• A Phase II Trial to Evaluate the Safety and Immunogenicity of Two Doses of a Folate Receptor Alpha Vaccine in Patients with Triple-Negative Breast Cancer

  2025cites this paper
• Dual roles of innate immune cells and cytokines in shaping the breast cancer microenvironment

  2025cites this paper
• Transcriptomic Signatures of Monocyte‐Derived Macrophages Associate With Androgen Receptor Pathway Inhibitor Progression in Prostate Cancer

  2025cites this paper
• Immune Evasion in Cancer Metastasis: An Unappreciated Role of Monocytes

  2025cites this paper
• Breast Cancer and Tumor Microenvironment: The Crucial Role of Immune Cells

  2025cites this paper
• Prognostic relevance of CD163+ immune cells in patients with metastatic breast cancer

  2025cites this paper
• A new method for handling heterogeneous data in bioinformatics

  2024cites this paper
• Myeloid-derived suppressor cells in cancer and cancer therapy

  2024cites this paper
• Myeloid-derived suppressor cells in cancer: Current knowledge and future perspectives.

  2024cites this paper
• Increased blood CSF3R+ myeloid-derived suppressor cell is a predictor for breast cancer recurrence.

  2024cites this paper
• An Open-Label Study of Subcutaneous CpG Oligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer

  2024cites this paper
• Protein Signature Differentiating Neutrophils and Myeloid-Derived Suppressor Cells Determined Using a Human Isogenic Cell Line Model and Protein Profiling

  2024cites this paper
• Peripheral immune cells in metastatic breast cancer patients display a systemic immunosuppressed signature consistent with chronic inflammation

  2024cites this paper
• MDSC expansion during HIV infection: regulators, ART and immune reconstitution

  2024cites this paper
• Phenotypic Analysis of Circulating Myeloid Derived Suppressor Cells and Their Subpopulations in Egyptian Females with Breast Cancer: A Single-Centre Case-Control Study

  2024cites this paper
• Deciphering the roles of myeloid derived suppressor cells in viral oncogenesis

  2023cites this paper
• Engineered Adoptive T-Cell Therapies for Breast Cancer: Current Progress, Challenges, and Potential

  2023cites this paper
• Identification of ZIP8-induced ferroptosis as a major type of cell death in monocytes under sepsis conditions

  2023cites this paper
• Myeloid-derived suppressor cells in head and neck squamous cell carcinoma.

  2023cites this paper
• Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells

  2023cites this paper
• Prognostic Implications of MALAT1 and BACH1 Expression and Their Correlation with CTCs and Mo-MDSCs in Triple Negative Breast Cancer and Surgical Management Options

  2022cites this paper
• IMMUNOLOGICAL FEATURES OF BREAST CANCER

  2022cites this paper
• Anti-Inflammatory Mechanisms of Dietary Flavones: Tapping into Nature to Control Chronic Inflammation in Obesity and Cancer

  2022cites this paper
• Reprogramming of myeloid cells and their progenitors in patients with non-medullary thyroid carcinoma

  2022cites this paper
• Breast cancers co-opt normal mechanisms of tolerance to promote immune evasion and metastasis.

  2022cites this paper
• Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood

  2022cites this paper
• New Perspectives on Myeloid-Derived Suppressor Cells and Their Emerging Role in Haematology

  2022cites this paper
• Flow cytometry-based Immunophenotyping of myeloid-derived suppressor cells in human breast cancer patient blood samples.

  2022cites this paper
• Phenotypic and functional heterogeneity of monocytes in health and cancer in the era of high dimensional technologies.

  2022cites this paper
• Circulating inflammatory cells in patients with metastatic breast cancer: Implications for treatment

  2022cites this paper
• Immune Lymphocyte Infiltrate and its Prognostic Value in Triple-Negative Breast Cancer

  2022cites this paper
• Sulfatase-2 from Cancer Associated Fibroblasts: An Environmental Target for Hepatocellular Carcinoma?

  2022cites this paper
• Myeloid-Derived Suppressor–Cell Dynamics Control Outcomes in the Metastatic Niche

  2022cites this paper
• Peripheral Blood Mononuclear Cell Populations Correlate with Outcome in Patients with Metastatic Breast Cancer

  2022influential citation
• Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients

  2022cites this paper
• Potential Predictive and Prognostic Value of Biomarkers Related to Immune Checkpoint Inhibitor Therapy of Triple-Negative Breast Cancer

  2022cites this paper
• Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1

  2022cites this paper
• Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases

  2022cites this paper
• Beyond Immunosuppression: The Multifaceted Functions of Tumor-Promoting Myeloid Cells in Breast Cancers

  2022cites this paper
• Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity

  2022cites this paper
• Crosstalk between Tumor-Infiltrating Immune Cells and Cancer-Associated Fibroblasts in Tumor Growth and Immunosuppression of Breast Cancer

  2021cites this paper
• Monocyte Regulation in Homeostasis and Malignancy.

  2021cites this paper
• Epithelial-to-mesenchymal Transition Heterogeneity of Circulating Tumor Cells and Their Correlation With MDSCs and Tregs in HER2-negative Metastatic Breast Cancer Patients

  2021cites this paper
• Tumor-related stress regulates functional plasticity of MDSCs.

  2021cites this paper
• Understanding breast cancer heterogeneity through non-genetic heterogeneity

  2021cites this paper
• Melatonin decreases metastasis, primary tumor growth and angiogenesis in a mice model of breast cancer

  2021cites this paper
• Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer

  2021cites this paper
• NFκB-Activated COX2/PGE2/EP4 Axis Controls the Magnitude and Selectivity of BCG-Induced Inflammation in Human Bladder Cancer Tissues

  2021cites this paper
• The Peripheral Immune Landscape of Breast Cancer: Clinical Findings and In Vitro Models for Biomarker Discovery

  2021cites this paper
• Bruton’s tyrosine kinase: an emerging targeted therapy in myeloid cells within the tumor microenvironment

  2021cites this paper
• Reanalysis of Non-Small-Cell Lung Cancer Microarray Gene Expression Data

  2021cites this paper
• Temporal Changes in Immune Responses within the Tumor Microenvironment in the 4T1.2-HER2 Mammary Tumor Model

  2021cites this paper
• Myeloid-derived suppressor cells regulate the immunosuppressive functions of PD-1−PD-L1+ Bregs through PD-L1/PI3K/AKT/NF-κB axis in breast cancer

  2021cites this paper
• Characteristics and Spatially Defined Immune (micro)landscapes of Early-stage PD-L1–positive Triple-negative Breast Cancer

  2021cites this paper
• Radiotherapy and Immunotherapy Combinations in the Treatment of Patients with Metastatic Disease: Current Status and Future Focus

  2021cites this paper
• Comparing the frequency of CD33+ pSTAT3+ myeloid‐derived suppressor cells and IL‐17+ lymphocytes in patients with prostate cancer and benign prostatic hyperplasia

  2021cites this paper
• Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer

  2021cites this paper
• Immune System Effects on Breast Cancer

  2021cites this paper
• Interactions Networks for Primary Heart Sarcomas

  2021cites this paper
• Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment

  2021cites this paper
• Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer

  2021cites this paper
• Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer

  2021cites this paper
• Innate immunity and metal ion trafficking pathway perturbations in idiopathic Parkinson's disease and Tuberculosis: A comparative transcriptomics approach

  2021cites this paper
• DEHP mediates drug resistance by directly targeting AhR in human breast cancer.

  2021cites this paper
• Systemic Influences of Mammary Cancer on Monocytes in Mice

  2021cites this paper
• 1 Characteristics and spatially-defined immune (micro)landscapes of early-stage PD-L1-positive triple-negative breast cancer

  2021cites this paper
• Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer

  2020cites this paper
• Platform-independent approach for cancer detection from gene expression profiles of peripheral blood cells

  2020cites this paper
• Do nature of bacteremia and origin of secondary sepsis in critically ill patients determine subset of myeloid-derived suppressor cells expansion?

  2020cites this paper
• Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

  2020cites this paper
• CD163+ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

  2020cites this paper
• The Generation and Identity of Human Myeloid-Derived Suppressor Cells

  2020cites this paper
• Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells

  2020cites this paper
• Clinical relevance of systemic monocytic-MDSCs in patients with metastatic breast cancer

  2020cites this paper
• Corrigendum: Myeloid-Derived Suppressor Cells Recruited by Chemokine (C-C Motif) Ligand 3 Promote the Progression of Breast Cancer via Phosphoinositide 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling

  2020cites this paper
• NOX2-Derived Reactive Oxygen Species in Cancer

  2020cites this paper
• Role of tumor microenvironment in the efficacy of BCG therapy

  2020cites this paper
• Predominance of M1 subtype among tumor-associated macrophages in phenotypically aggressive sporadic vestibular schwannoma.

  2020cites this paper
• Mitohormesis reprograms macrophage metabolism to enforce tolerance

  2020cites this paper
• TIME Is a Great Healer—Targeting Myeloid Cells in the Tumor Immune Microenvironment to Improve Triple-Negative Breast Cancer Outcomes

  2020cites this paper
• Systemic Reprogramming of Monocytes in Cancer

  2020influential citation
• Recent advances in myeloid-derived suppressor cell biology

  2020cites this paper
• Applying Osteosarcoma Immunology to Understand Disease Progression and Assess Immunotherapeutic Response.

  2020cites this paper
• The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

  2020cites this paper
• Myeloid-Derived Suppressor Cells Recruited by Chemokine (C-C Motif) Ligand 3 Promote the Progression of Breast Cancer via Phosphoinositide 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling

  2020cites this paper
• Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment.

  2020cites this paper
• Selectively hampered activation of lymph node-resident dendritic cells precedes profound T cell suppression and metastatic spread in the breast cancer sentinel lymph node

  2019cites this paper
• The CD14+HLA-DRlo/neg Monocyte: An Immunosuppressive Phenotype That Restrains Responses to Cancer Immunotherapy

  2019cites this paper
• Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared between tuberculosis and rheumatoid arthritis

  2019cites this paper
• Deciphering myeloid-derived suppressor cells: isolation and markers in humans, mice and non-human primates

  2019cites this paper
• The role of 2-arachidonoylglycerol in the regulation of the tumor-immune microenvironment in murine models of pancreatic cancer.

  2019cites this paper
• The breast tumour microenvironment (cid:884) role in cancer development, progression and response to therapy

  2019cites this paper
• The balance between breast cancer and the immune system: challenges for prognosis and clinical benefit from immunotherapies.

  2019cites this paper
• Frequency of Immune Cell Subtypes in Peripheral Blood Correlates With Outcome for Patients With Metastatic Breast Cancer Treated With High-Dose Chemotherapy.

  2019cites this paper
• Impact of systemic therapy on circulating leukocyte populations in patients with metastatic breast cancer

  2019cites this paper
• Innate Immune Determinants of Graft-Versus-Host Disease and Bidirectional Immune Tolerance in Allogeneic Transplantation

  2019cites this paper
• Visualization and quantification of in vivo homing kinetics of myeloid-derived suppressor cells in primary and metastatic cancer

  2019cites this paper
• Redox reactions in cancer: impact and regulation

  2018cites this paper