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Updated: Aug 22, 2025

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
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Self-Renewal of Macrophages: Tumor-Released Factors and Signaling Pathways

Serena Filiberti1, Mariapia Russo1, Silvia Lonardi2

  • 1Department of Biotechnology Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.

Biomedicines
|November 11, 2022
PubMed

Insights

Tumor-associated macrophages (TAMs) are key immune cells in cancer. This review explores how environmental factors and metabolism influence TAM self-renewal and proliferation, offering potential new anticancer targets.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Metabolism

Background:

  • Macrophages are abundant immune cells in the tumor microenvironment (TME).
  • Tumor-associated macrophages (TAMs) arise from resident macrophages and monocytes, correlating with poor prognosis in most cancers.
  • Macrophage plasticity and self-renewal significantly impact tumor progression and therapy resistance.

Purpose of the Study:

  • To review environmental factors promoting macrophage self-renewal.
  • To elucidate molecular mechanisms governing TAM proliferation.
  • To highlight the influence of tumor-derived factors on macrophage metabolism and its effect on self-renewal.

Main Methods:

  • Literature review focusing on macrophage self-renewal and proliferation in cancer.
  • Analysis of signaling pathways regulating TAMs.
  • Investigation of metabolic pathways affecting macrophage functions.

Main Results:

  • Environmental factors critically influence macrophage self-renewal capacity.
  • Tumor-derived factors alter macrophage metabolism, impacting proliferation and subset functions.
  • Specific molecular and metabolic pathways are identified as key regulators of TAM self-renewal.

Conclusions:

  • Understanding TAM self-renewal mechanisms is crucial for cancer therapy.
  • Targeting signaling pathways and metabolic reprogramming in TAMs may lead to novel anticancer strategies.
  • Macrophage plasticity and metabolism are central to tumor progression and therapeutic resistance.
Keywords:
metabolic signatureproliferationself-renewalsignaling pathwaystumor-associated macrophages

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