Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy.
Oncotarget
; 7(48): 78653-78666, 2016 Nov 29.
Article
en En
| MEDLINE
| ID: mdl-27602953
ABSTRACT
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, TGFß 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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tirosina Quinasa c-Mer
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Macrófagos
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Recurrencia Local de Neoplasia
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Neoplasias Experimentales
Límite:
Animals
Idioma:
En
Revista:
Oncotarget
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos