Macrophage Polarization States in the Tumor Microenvironment

Int J Mol Sci. 2021 Jun 29;22(13):6995. doi: 10.3390/ijms22136995.


The M1/M2 macrophage paradigm plays a key role in tumor progression. M1 macrophages are historically regarded as anti-tumor, while M2-polarized macrophages, commonly deemed tumor-associated macrophages (TAMs), are contributors to many pro-tumorigenic outcomes in cancer through angiogenic and lymphangiogenic regulation, immune suppression, hypoxia induction, tumor cell proliferation, and metastasis. The tumor microenvironment (TME) can influence macrophage recruitment and polarization, giving way to these pro-tumorigenic outcomes. Investigating TME-induced macrophage polarization is critical for further understanding of TAM-related pro-tumor outcomes and potential development of new therapeutic approaches. This review explores the current understanding of TME-induced macrophage polarization and the role of M2-polarized macrophages in promoting tumor progression.

Keywords: cytokine signaling; malignancy; metastasis; polarization; tumor microenvironment; tumor-associated macrophage.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism
  • Cytokines / metabolism
  • Humans
  • Hypoxia / genetics
  • Hypoxia / immunology
  • Hypoxia / metabolism
  • Immunophenotyping
  • Inflammation / etiology
  • Inflammation / metabolism
  • Macrophage Activation / genetics
  • Macrophage Activation / immunology*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Signal Transduction
  • Tumor Microenvironment / immunology*
  • Tumor-Associated Macrophages / immunology*
  • Tumor-Associated Macrophages / metabolism*
  • Tumor-Associated Macrophages / pathology


  • Biomarkers
  • Cytokines