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TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting

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  1. Exercise Oncology and Immuno-Oncology; A (Future) Dynamic Duo

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  2. Expansion With IL-15 Increases Cytotoxicity of Vγ9Vδ2 T Cells and Is Associated With Higher Levels of Cytotoxic Molecules and T-bet

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  3. Inflammation induced PD-L1-specific T cells

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  4. MERTK Acts as a Costimulatory Receptor on Human CD8+ T Cells

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The TAM receptors-TYRO3, AXL, MERTK-are pleiotropically expressed receptors in both healthy and diseased tissue. A complex of the ligands Protein S (PROS1) or Growth Arrest-Specific 6 (GAS6) with apoptotic phosphatidylserine activates the TAM receptors. Hence, this receptor family is essential for the efferocytosis of apoptotic material by antigen-presenting cells. In addition, TAM receptors are expressed by virtually all cells of the tumor microenvironment. They are also potent oncogenes, frequently overexpressed in cancer and involved in survival and therapy resistance. Due to their pro-oncogenic and immune-inhibitory traits, TAM receptors have emerged as promising targets for cancer therapy. Recently, TAM receptors have been described to function as costimulatory molecules on human T cells. TAM receptors' ambivalent functions on many different cell types therefore make therapeutic targeting not straight-forward. In this review we summarize our current knowledge of the function of TAM receptors in the tumor microenvironment. We place particular focus on TAM receptors and the recently unraveled role of MERTK in activated T cells and potential consequences for anti-tumor immunity.

Original languageEnglish
JournalCancer immunology, immunotherapy : CII
ISSN0340-7004
DOIs
Publication statusPublished - 29 Oct 2019

ID: 58521903