Elevated levels of polymorphonuclear myeloid-derived suppressor cells in patients with glioblastoma highly express S100A8/9 and arginase and suppress T cell function
| Autor: | Gosse J. Adema, Mark ter Laan, Pieter Wesseling, Sandra A. J. F. H. Bossman, Barbara M Schulte, Kiek Verrijp, Esther D. Kers-Rebel, Paul R Gielen |
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| Přispěvatelé: | Pathology, CCA - Biomarkers |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research T-Lymphocytes Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] medicine.medical_treatment T cell Clinical Neurology MDSCs Review Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] Lymphocyte Activation S100A8 Flow cytometry 03 medical and health sciences 0302 clinical medicine Basic and Translational Investigation Glioma glioma Biomarkers Tumor Tumor Cells Cultured medicine Journal Article Calgranulin B Humans Calgranulin A Medicine(all) Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] medicine.diagnostic_test Brain Neoplasms business.industry Myeloid-Derived Suppressor Cells arginase S100A8/9 Immunotherapy medicine.disease Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] Arginase 030104 developmental biology Cytokine medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Immunology Myeloid-derived Suppressor Cell Neurology (clinical) Glioblastoma business Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] |
| Zdroj: | Gielen, P R, Schulte, B M, Kers-Rebel, E D, Verrijp, K, Bossman, S A J F H, Ter Laan, M, Wesseling, P & Adema, G J 2016, ' Elevated levels of polymorphonuclear myeloid-derived suppressor cells in patients with glioblastoma highly express S100A8/9 and arginase and suppress T cell function ', Neuro-Oncology, vol. 18, no. 9, pp. 1253-64 . https://doi.org/10.1093/neuonc/now034 Neuro-Oncology, 18(9), 1253-64. Oxford University Press Neuro-Oncology, 18, 9, pp. 1253-64 Neuro-Oncology, 18, 1253-64 Neuro-Oncology, 18(9), 1253. Oxford University Press |
| ISSN: | 1522-8517 |
| DOI: | 10.1093/neuonc/now034 |
| Popis: | Contains fulltext : 167769.pdf (Publisher’s version ) (Closed access) BACKGROUND: Gliomas 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). METHODS: We 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. RESULTS: We 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. CONCLUSIONS: These 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. |
| Databáze: | OpenAIRE |
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