Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy
Metrics: PDF 1234 views | HTML 2604 views | ?
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
Michael J. Gough, email: email@example.com
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.