TY - JOUR
T1 - TAM-ing T cells in the tumor microenvironment
T2 - implications for TAM receptor targeting
AU - Peeters, Marlies J.W.
AU - Rahbech, Anne
AU - thor Straten, Per
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
KW - CITIM 2019
KW - Costimulation
KW - MERTK
KW - PROS1
KW - T lymphocytes
KW - TAM receptors
U2 - 10.1007/s00262-019-02421-w
DO - 10.1007/s00262-019-02421-w
M3 - Review
C2 - 31664482
AN - SCOPUS:85074629867
SN - 0340-7004
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
ER -
