Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth

Int J Mol Sci. 2021 Jun 18;22(12):6526. doi: 10.3390/ijms22126526.

Abstract

Breast cancer is the most commonly occurring cancer in women of Western countries and is the leading cause of cancer-related mortality. The breast tumor microenvironment contains immune cells, fibroblasts, adipocytes, mesenchymal stem cells, and extracellular matrix. Among these cells, macrophages or tumor-associated macrophages (TAMs) are the major components of the breast cancer microenvironment. TAMs facilitate metastasis of the breast tumor and are responsible for poor clinical outcomes. High TAM density was also found liable for the poor prognosis of breast cancer. These observations make altering TAM function a potential therapeutic target to treat breast cancer. The present review summarizes the origin of TAMs, mechanisms of macrophage recruitment and polarization in the tumor, and the contributions of TAMs in tumor progression. We have also discussed our current knowledge about TAM-targeted therapies and the roles of miRNAs and exosomes in re-educating TAM function.

Keywords: angiogenesis; breast cancer; exosomes; immunosuppression; macrophage polarization; metastasis; miRNA; tumor microenvironment; tumor-associated macrophages.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / therapy
  • Cell Communication
  • Disease Progression
  • Disease Susceptibility
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunomodulation
  • Macrophage Activation / immunology
  • MicroRNAs / genetics
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / metabolism
  • Tumor Burden
  • Tumor Microenvironment*
  • Tumor-Associated Macrophages / immunology*
  • Tumor-Associated Macrophages / metabolism*
  • Tumor-Associated Macrophages / pathology

Substances

  • Biomarkers, Tumor
  • MicroRNAs