Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium.
Mol Carcinog
; 57(11): 1664-1671, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30035346
ABSTRACT
Solid tumors are covered by stroma, which is hypoxic in nature and composed of various non-malignant components such as endothelial cells, fibroblasts, and pericytes that support tumor growth. Tumor stroma represents a mechanical barrier for tumor infiltration of CD8+ effector T cells in particular. In this context, our previous studies have demonstrated the therapeutic impact of Low-Dose Radiation (LDR)-primed and M1-retuned (iNOS+) peritumoral macrophages that produce inducible nitric oxide, have immunological roles on tumor infiltration of effector T cells, cancer-related inflammation, and subsequent tumor immune rejection in a mouse model of pancreatic cancer. These findings suggested a possible modification of tumor endothelium by LDR-primed macrophages. In line with these observations, here we demonstrate the influence of LDR in down-modulating HIF-1 in irradiated tumors in the course of polarization of irradiated tumor-associated macrophages toward an M1 phenotype. Furthermore, we demonstrate that M1 macrophages which are primed by LDR can directly influence angiogenic responses in eNOS+ endothelial cells which produce nitric oxide having both vascular and physiological roles. Furthermore, we demonstrate that naïve macrophages, upon differentiating to an M1 phenotype either by Th1 stimuli or LDR, potentially modify sphingosine-1-phosphate/VEGF-induced angiogenic signaling in tumor-derived endothelial cells with tumorigenic potential, thus indicating the significance of iNOS+ macrophages in modulating signaling in eNOS+ tumor-derived endothelium. Our study suggests that iNOS+ macrophages can activate tumor endothelium which may contribute to cancer-directed immunotherapy in particular.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Radiación Ionizante
/
Endotelio Vascular
/
Óxido Nítrico Sintasa de Tipo II
/
Macrófagos
/
Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
India