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

Research output: Contribution to journalReview article

Abstract

Tumor-associated macrophages are an abundant cell type in the tumor microenvironment. These macrophages serve as a promising target for treatment of cancer due to their roles in promoting cancer progression and simultaneous immunosuppression. The TAM receptors (Tyro3, Axl and MerTK) are promising therapeutic targets on tumor-associated macrophages. The TAM receptors are a family of receptor tyrosine kinases with shared ligands Gas6 and Protein S that skew macrophage polarization towards a pro-tumor M2-like phenotype. In macrophages, the TAM receptors also promote apoptotic cell clearance, a tumor-promoting process called efferocytosis. The TAM receptors bind the "eat-me" signal phosphatidylserine on apoptotic cell membranes using Gas6 and Protein S as bridging ligands. Post-efferocytosis, macrophages are further polarized to a pro-tumor M2-like phenotype and secrete increased levels of immunosuppressive cytokines. Since M2 polarization and efferocytosis are tumor-promoting processes, the TAM receptors on macrophages serve as exciting targets for cancer therapy. Current TAM receptor-directed therapies in preclinical development and clinical trials may have anti-cancer effects though impacting macrophage phenotype and function in addition to the cancer cells.

Original languageEnglish (US)
Article number94
JournalMolecular Cancer
Volume18
Issue number1
DOIs
StatePublished - May 14 2019

Keywords

  • Axl
  • Efferocytosis
  • M2 macrophage polarization
  • Macrophage
  • MerTK
  • TAM receptors
  • Tyro3

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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