Research Papers:

Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy

Marka R. Crittenden, Jason Baird, David Friedman, Talicia Savage, Lauren Uhde, Alejandro Alice, Benjamin Cottam, Kristina Young, Pippa Newell, Cynthia Nguyen, Shelly Bambina, Gwen Kramer, Emmanuel Akporiaye, Anna Malecka, Andrew Jackson and Michael J. Gough _

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Oncotarget. 2016; 7:78653-78666. https://doi.org/10.18632/oncotarget.11823

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Marka R. Crittenden1,2, Jason Baird1, David Friedman1, Talicia Savage1, Lauren Uhde1, Alejandro Alice1, Benjamin Cottam1, Kristina Young1,2, Pippa Newell1,3, Cynthia Nguyen1, Shelly Bambina1, Gwen Kramer1, Emmanuel Akporiaye1, Anna Malecka4, Andrew Jackson4, Michael J. Gough1

1Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland OR, USA

2The Oregon Clinic, Portland OR, USA

3Providence Hepatobiliary and Pancreatic Cancer Program, Providence Portland Medical Center, Portland OR, USA

4Host-Tumour Interactions Group, Division of Cancer and Stem Cells, University of Nottingham, UK

Correspondence to:

Michael J. Gough, email: [email protected]

Keywords: radiation, macrophage, tumor, phagocytosis, apoptosis

Received: July 16, 2016    Accepted: August 25, 2016    Published: September 2, 2016


Radiation therapy provides a means to kill large numbers of cancer cells in a controlled location resulting in the release of tumor-specific antigens and endogenous adjuvants. However, by activating pathways involved in apoptotic cell recognition and phagocytosis, irradiated cancer cells engender suppressive phenotypes in macrophages. We demonstrate that the macrophage-specific phagocytic receptor, Mertk is upregulated in macrophages in the tumor following radiation therapy. Ligation of Mertk on macrophages results in anti-inflammatory cytokine responses via NF-kB p50 upregulation, which in turn limits tumor control following radiation therapy. We demonstrate that in immunogenic tumors, loss of Mertk is sufficient to permit tumor cure following radiation therapy. However, in poorly immunogenic tumors, TGFβ inhibition is also required to result in tumor cure following radiation therapy. These data demonstrate that Mertk is a highly specific target whose absence permits tumor control in combination with radiation therapy.

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