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Macrophage–tumor crosstalk: role of TAMR tyrosine kinase receptors and of their ligands

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Abstract

Ample clinical and preclinical evidence indicates that macrophages interact with tumor cells as well as with virtually all populations of host cells present in the tumor microenvironment. This crosstalk can strongly promote malignancy, but also has in principle the potential to inhibit tumor growth. Thus, it is of the utmost importance to improve our understanding of the mechanisms driving the pro- and antimalignant behavior of tumor-associated macrophages (TAMs) in order to develop better anticancer therapies. In this review, we discuss the biological consequences of reciprocal interactions between TAMs, cancer cells, endothelial cells, fibroblasts and other leukocyte subfractions within tumors. It was recently elucidated that tumors specifically educate macrophages to secrete growth arrest-specific gene 6 (Gas6), the common ligand of the Tyro3, Axl, Mer receptor (TAMR) family. In turn, Gas6 fosters tumor growth by promoting cancer cell proliferation. Therefore, the Gas6–TAMR axis might represent a novel target for disrupting tumor–macrophage crosstalk. We summarize here what is known about TAMR and their ligands in (human) cancer biology. In order to shed more light on the role of macrophages in human cancer, we additionally provide an overview of what is currently known about the prognostic impact of TAMs in human cancer.

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Acknowledgments

S.L. is funded by the Max-Eder group leader program of the Deutsche Krebshilfe, by the Hamburger Krebsgesellschaft and by the Roggenbuck Stiftung. A.S. receives funding from the Roggenbuck Stiftung.

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Authors and Affiliations

  1. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    Thomas Schmidt

  2. Department of Hematology and Oncology with Sections BMT and Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Isabel Ben-Batalla, Alexander Schultze & Sonja Loges

  3. Institute of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Isabel Ben-Batalla, Alexander Schultze & Sonja Loges

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Thomas Schmidt and Isabel Ben-Batalla contributed equally to this work.

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Schmidt, T., Ben-Batalla, I., Schultze, A. et al. Macrophage–tumor crosstalk: role of TAMR tyrosine kinase receptors and of their ligands. Cell. Mol. Life Sci. 69, 1391–1414 (2012). https://doi.org/10.1007/s00018-011-0863-7

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