Tumors induce the formation of suppressor endothelial cells in vivo |
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Authors: | Jennifer Konopa Mulligan M Rita I Young |
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Institution: | (1) Research Service, Ralph H. Johnson VA Medical Center, 109 Bee Street, Charleston, SC 29401, USA;(2) Department of Otolaryngology, Medical University of South Carolina, Charleston, SC, USA;(3) Department of Medicine, Medical University of South Carolina, Charleston, SC, USA |
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Abstract: | Patients with solid tumors have defects in immune effector cells, which have been associated with a poorer prognosis. Previous
studies by our laboratory have shown that exposure to Lewis lung carcinoma (LLC)-secreted products induces the formation of
suppressor endothelial cells in vitro. The current studies examined if tumors could induce the formation of suppressor endothelial
cells in vivo. Endothelial cells were immunomagnetically isolated from the lungs of tumor-bearing mice or normal controls
and examined for their ability to modulate NK cell, T-cell and macrophage functions. Compared to normal controls, supernatants
from endothelial cells isolated from tumor-bearing lungs had elevated secretion of PGE2, IL-6, IL-10 and VEGF. Conditioned media from endothelial cells isolated from normal lungs increased CD8+ T-cell IFN-γ and CD4+ T-cell IL-2 production in response to anti-CD3 stimulation, while media conditioned by endothelial cells from tumor-bearing
lungs had a diminished stimulatory capacity. Examination of NK cell functions showed that supernatants from endothelial cells
isolated from normal lungs were potent activators of NK cells, as indicated by their secretion of TNF-α and IFN-γ. Endothelial
cells isolated from tumor-bearing lungs had a significantly diminished capacity to activate NK cells. Finally, supernatants
from endothelial cells of tumor-bearing lungs diminished macrophage phagocytosis compared to either treatment with supernatants
of normal endothelial cells or treatment with media alone. The results of these studies demonstrate that tumors induce the
formation of suppressor endothelial cells in vivo and provide support for the role of endothelial cells in tumor-induced immune
suppression. |
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