• Paul R Gielen, Barbara M Schulte, Esther D Kers-Rebel, Kiek Verrijp, Sandra A J F H Bossman, Mark Ter Laan, Pieter Wesseling, and Gosse J Adema.
• Tumor Immunology Laboratory, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands (P.R.G., B.M.S., E.D.K.-R., G.J.A.); Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands (K.V., P.W.); Department of Neurosurgery, Radboud University Medical Center, Nijmegen, the Netherlands (S.A.J.H.B., M.L.); Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands (P.W.).
• Neuro-oncology. 2016 Sep 1; 18 (9): 1253-64.

BackgroundGliomas are primary brain tumors that are associated with a poor prognosis. The introduction of new treatment modalities (including immunotherapy) for these neoplasms in the last 3 decades has resulted in only limited improvement in survival. Gliomas are known to create an immunosuppressive microenvironment that hampers the efficacy of (immuno)therapy. One component of this immunosuppressive environment is the myeloid-derived suppressor cell (MDSC).MethodsWe set out to analyze the presence and activation state of MDSCs in blood (n = 41) and tumor (n = 20) of glioma patients by measuring S100A8/9 and arginase using flow cytometry and qPCR. Inhibition of T cell proliferation and cytokine production after stimulation with anti-CD3/anti-CD28 coated beads was used to measure in vitro MDSC suppression capacity.ResultsWe report a trend toward a tumor grade-dependent increase of both monocytic (M-) and polymorphonuclear (PMN-) MDSC subpopulations in the blood of patients with glioma. M-MDSCs of glioma patients have increased levels of intracellular S100A8/9 compared with M-MDSCs in healthy controls (HCs). Glioma patients also have increased S100A8/9 serum levels, which correlates with increased arginase activity in serum. PMN-MDSCs in both blood and tumor tissue demonstrated high expression of arginase. Furthermore, we assessed blood-derived PMN-MDSC function and showed that these cells have potent T cell suppressive function in vitro.ConclusionsThese data indicate a tumor grade-dependent increase of MDSCs in the blood of patients with a glioma. These MDSCs exhibit an increased activation state compared with MDSCs in HCs, independent of tumor grade.© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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