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Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment
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Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment
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Journal Article
Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment
2019
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Animals
/ Axl
/ Axl Receptor Tyrosine Kinase
/ B cells
/ Biomedical and Life Sciences
/ c-Mer Tyrosine Kinase - metabolism
/ Cancer
/ Disease
/ Humans
/ Kinases
/ Ligands
/ MerTK
/ Oncology
/ Phenols (Class of compounds)
/ Protein Kinase Inhibitors - pharmacology
/ Protein Kinase Inhibitors - therapeutic use
/ Protein-tyrosine kinase receptors
/ Proteins
/ Proto-Oncogene Proteins - metabolism
/ Receptor Protein-Tyrosine Kinases - antagonists & inhibitors
/ Receptor Protein-Tyrosine Kinases - metabolism
/ Review
/ Roles
/ Tumor Microenvironment - drug effects
/ Tumors
/ Tyro3
/ Tyrosine
