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29.10.2019 | Focussed Research Review Open Access

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

Cancer Immunology, Immunotherapy
Marlies J. W. Peeters, Anne Rahbech, Per thor Straten
Wichtige Hinweise
This paper is a Focussed Research Review based on a presentation given at the Sixth International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2019), held in Tbilisi, Georgia, 29th April–2nd May 2019. It is part of a series of CITIM 2019 papers in Cancer Immunology, Immunotherapy.

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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.

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