Tumor-infiltrating, myeloid-derived suppressor cells inhibit T cell activity by nitric oxide production in an intracranial rat glioma + vaccination model.
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.
Jia
Wentao
W
Department of Neurosurgery, Virginia Commonwealth, Richmond, VA 23298-0631, USA.
Jackson-Cook
Colleen
C
Graf
Martin R
MR
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014611:Vaccination
D019496:Cancer Vaccines; D009569:Nitric Oxide
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