TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting
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 t...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2020-02, Vol.69 (2), p.237-244 |
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| creator | Peeters, Marlies J. W. Rahbech, Anne thor Straten, Per |
| description | 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. |
| doi_str_mv | 10.1007/s00262-019-02421-w |
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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. 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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. 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W.</au><au>Rahbech, Anne</au><au>thor Straten, Per</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>69</volume><issue>2</issue><spage>237</spage><epage>244</epage><pages>237-244</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>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. 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| ispartof | Cancer Immunology, Immunotherapy, 2020-02, Vol.69 (2), p.237-244 |
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| subjects | Animals Antigen-presenting cells Antineoplastic Agents - pharmacology Apoptosis Axl protein Axl Receptor Tyrosine Kinase Biomarkers c-Mer Tyrosine Kinase - genetics c-Mer Tyrosine Kinase - metabolism Cancer Research Costimulator Focussed Research Review Humans Immunology Lymphocytes Lymphocytes T Medicine Medicine & Public Health Molecular Targeted Therapy Neoplasms - drug therapy Neoplasms - etiology Neoplasms - metabolism Neoplasms - pathology Oncology Phosphatidylserine Protein S Protein-tyrosine kinase receptors Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Receptor mechanisms Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Signal Transduction T-Lymphocytes - immunology T-Lymphocytes - metabolism Therapeutic targets Tumor Microenvironment - drug effects Tumor Microenvironment - genetics Tumor Microenvironment - immunology |
| title | TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting |
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