Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 223, Issue 1-2, Pages 20-30Publisher
ELSEVIER
DOI: 10.1016/j.jneuroim.2010.03.011
Keywords
Brain tumor-associated immunosuppression; Malignant glioma; Myeloid-derived suppressor cells; Nitric oxide
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Funding
- James and Martha Betts Foundation
- National Cancer Institute at the National Institutes of Health [5R01CA116695]
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In rats bearing an intracranial T9 glioma, immunization with tumor antigens induces myeloid suppressor cells, which express neutrophil (His48) and monocyte (CD11bc) markers, to infiltrate the tumors. The His48(+)/CD11bc(+) cells were not derived from CNS microglia but were hematogenous; suppressed multiple T cell effector functions; and are myeloid-derived suppressor cells (MDSC). The glioma-infiltrating MDSC expressed arginase I, iNOS, indoleamine 2,3-dioxygenase and TGF-beta; however, inhibitor/blocking studies demonstrated that NO production was the primary mechanism of suppression which induced T cell apoptosis. These findings suggest that neuro-immunomodulation by MDSC in rat gliomas maybe mediated by a pathway requiring NO production. (C) 2010 Elsevier B.V. All rights reserved.
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