Journal Article

Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties

Jennifer C. Rodrigues, Guido C. Gonzalez, Lei Zhang, George Ibrahim, John J. Kelly, Michael P. Gustafson, Yi Lin, Allan B. Dietz, Peter A. Forsyth, V. Wee Yong and Ian F. Parney

in Neuro-Oncology

Published on behalf of Society for Neuro-Oncology

Volume 12, issue 4, pages 351-365
Published in print April 2010 | ISSN: 1522-8517
Published online December 2009 | e-ISSN: 1523-5866 | DOI:
Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties

More Like This

Show all results sharing these subjects:

  • Medical Oncology
  • Neurology


Show Summary Details


Glioblastoma patients are immunosuppressed, yet glioblastomas are highly infiltrated by monocytes/macrophages. Myeloid-derived suppressor cells (MDSC; immunosuppressive myeloid cells including monocytes) have been identified in other cancers and correlate with tumor burden. We hypothesized that glioblastoma exposure causes normal monocytes to assume an MDSC-like phenotype and that MDSC are increased in glioblastoma patients. Healthy donor human CD14+ monocytes were cultured with human glioblastoma cell lines. Controls were cultured alone or with normal human astrocytes. After 48 hours, glioblastoma-conditioned monocytes (GCM) were purified using magnetic beads. GCM cytokine and costimulatory molecular expression, phagocytic ability, and ability to induce apoptosis in activated lymphocytes were assessed. The frequency of MDSC was assessed by flow cytometry in glioma patients' blood and in GCM in vitro. As predicted, GCM have immunosuppressive, MDSC-like features, including reduced CD14 (but not CD11b) expression, increased immunosuppressive interleukin-10, transforming growth factor-β, and B7-H1 expression, decreased phagocytic ability, and increased ability to induce apoptosis in activated lymphocytes. Direct contact between monocytes and glioblastoma cells is necessary for complete induction of these effects. In keeping with our hypothesis, glioblastoma patients have increased circulating MDSC compared with normal donors and MDSC are increased in glioma-conditioned monocytes in vitro. To our knowledge, this has not been reported previously. Although further study is needed to directly characterize their origin and function in glioblastoma patients, these results suggest that MDSC may be an important contributor to systemic immunosuppression and can be modeled in vitro by GCM.

Keywords: B7-H1; immunosuppression; malignant glioma; monocyte; myeloid-derived suppressor cells

Journal Article.  6702 words.  Illustrated.

Subjects: Medical Oncology ; Neurology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.