Tumor-infiltrating, myeloid-derived suppressor cells inhibit T cell activity by nitric oxide production in an intracranial rat glioma + vaccination model

J Neuroimmunol. 2010 Jun;223(1-2):20-30. doi: 10.1016/j.jneuroim.2010.03.011. Epub 2010 May 8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • Coculture Techniques
  • Disease Models, Animal
  • Female
  • Glioma / immunology*
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Nitric Oxide* / biosynthesis
  • Rats
  • Rats, Inbred F344
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*
  • Vaccination

Substances

  • Cancer Vaccines
  • Nitric Oxide