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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Review

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

Authors: Kayla V. Myers, Sarah R. Amend, Kenneth J. Pienta

Published in: Molecular Cancer | Issue 1/2019

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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.
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Metadata
Title
Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment
Authors
Kayla V. Myers
Sarah R. Amend
Kenneth J. Pienta
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1022-2

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