How Macrophages Become Transcriptionally Dysregulated: A Hidden Impact of Antitumor Therapy

Int J Mol Sci. 2021 Mar 6;22(5):2662. doi: 10.3390/ijms22052662.

Abstract

Tumor-associated macrophages (TAMs) are the essential components of the tumor microenvironment. TAMs originate from blood monocytes and undergo pro- or anti-inflammatory polarization during their life span within the tumor. The balance between macrophage functional populations and the efficacy of their antitumor activities rely on the transcription factors such as STAT1, NF-κB, IRF, and others. These molecular tools are of primary importance, as they contribute to the tumor adaptations and resistance to radio- and chemotherapy and can become important biomarkers for theranostics. Herein, we describe the major transcriptional mechanisms specific for TAM, as well as how radio- and chemotherapy can impact gene transcription and functionality of macrophages, and what are the consequences of the TAM-tumor cooperation.

Keywords: cancer; chemotherapy; immunotherapy; oncoimmunology; radiotherapy; transcription factors; tumor-associated macrophages.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Cytokines / metabolism
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Gene Expression Regulation, Neoplastic* / immunology
  • Gene Expression Regulation, Neoplastic* / radiation effects
  • Humans
  • Immunotherapy / adverse effects*
  • Inflammation
  • Interferon Regulatory Factors / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / radiotherapy
  • Radiotherapy / adverse effects*
  • STAT Transcription Factors / metabolism
  • Transcription, Genetic* / drug effects
  • Transcription, Genetic* / immunology
  • Transcription, Genetic* / radiation effects
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Tumor Microenvironment / radiation effects
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor-Associated Macrophages / drug effects*
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism
  • Tumor-Associated Macrophages / radiation effects*

Substances

  • Antineoplastic Agents
  • Cytokines
  • Interferon Regulatory Factors
  • NF-kappa B
  • Neoplasm Proteins
  • STAT Transcription Factors
  • TP53 protein, human
  • Tumor Suppressor Protein p53