Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy
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 su...
| Main Authors: | , , , , |
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| Format: | Article |
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Impact Journals
2016
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| Online Access: | https://eprints.nottingham.ac.uk/43203/ |
| _version_ | 1848796635256061952 |
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| author | Crittenden, Marka R. Baird, Jason Malecka, Anna Jackson, Andrew M. Gough, Michael J. |
| author_facet | Crittenden, Marka R. Baird, Jason Malecka, Anna Jackson, Andrew M. Gough, Michael J. |
| author_sort | Crittenden, Marka R. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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, TGFb 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. |
| first_indexed | 2025-11-14T19:51:07Z |
| format | Article |
| id | nottingham-43203 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:51:07Z |
| publishDate | 2016 |
| publisher | Impact Journals |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-432032020-05-04T18:13:49Z https://eprints.nottingham.ac.uk/43203/ Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy Crittenden, Marka R. Baird, Jason Malecka, Anna Jackson, Andrew M. Gough, Michael J. 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, TGFb 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. Impact Journals 2016-09-02 Article PeerReviewed Crittenden, Marka R., Baird, Jason, Malecka, Anna, Jackson, Andrew M. and Gough, Michael J. (2016) Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy. Oncotarget, 7 (48). pp. 78653-78666. ISSN 1949-2553 radiation macrophage tumor phagocytosis apoptosis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346667/ doi:10.18632/oncotarget.11823 doi:10.18632/oncotarget.11823 |
| spellingShingle | radiation macrophage tumor phagocytosis apoptosis Crittenden, Marka R. Baird, Jason Malecka, Anna Jackson, Andrew M. Gough, Michael J. Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy |
| title | Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy |
| title_full | Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy |
| title_fullStr | Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy |
| title_full_unstemmed | Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy |
| title_short | Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy |
| title_sort | mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy |
| topic | radiation macrophage tumor phagocytosis apoptosis |
| url | https://eprints.nottingham.ac.uk/43203/ https://eprints.nottingham.ac.uk/43203/ https://eprints.nottingham.ac.uk/43203/ |