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Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment

Kayla V Myers1,2, Sarah R Amend3, Kenneth J Pienta4,3,5,6

  • 1Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, MD, USA. kmyers38@jhmi.edu.

Molecular Cancer
|May 16, 2019
PubMed

Insights

Targeting TAM receptors on tumor-associated macrophages could be a novel cancer therapy. These receptors promote tumor growth by enhancing efferocytosis and M2 polarization, making them key targets for new treatments.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Tumor-associated macrophages (TAMs) are crucial in the tumor microenvironment, promoting cancer progression and immune suppression.
  • The TAM receptor tyrosine kinases (Tyro3, Axl, MerTK) are key regulators of TAM function.
  • TAM receptors mediate efferocytosis and skew macrophages towards a pro-tumor M2 phenotype via Gas6/Protein S ligands.

Purpose of the Study:

  • To highlight TAM receptors as promising therapeutic targets in cancer treatment.
  • To elucidate the role of TAM receptors in macrophage polarization and efferocytosis.
  • To discuss the potential of targeting TAM receptors for anti-cancer therapies.

Main Methods:

  • Review of existing literature on TAM receptors, ligands, and macrophage biology.
  • Analysis of the molecular mechanisms underlying TAM receptor signaling in macrophages.
  • Examination of preclinical and clinical data on TAM receptor-targeted therapies.

Main Results:

  • TAM receptors, activated by Gas6 and Protein S, promote efferocytosis of apoptotic cells.
  • Post-efferocytosis, TAM receptors further drive M2-like polarization and immunosuppression.
  • These processes contribute to tumor progression and immune evasion.

Conclusions:

  • TAM receptors are critical mediators of pro-tumor functions in macrophages.
  • Targeting TAM receptors offers a promising strategy for cancer therapy.
  • Modulating TAM receptor activity may impact both macrophage function and cancer cell behavior.
Keywords:
AxlEfferocytosisM2 macrophage polarizationMacrophageMerTKTAM receptorsTyro3

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