In a cohort of patients with benign, non-glial, or glial brain tumors, analysis of PBMCs by flow cytometry revealed a positive correlation between relative levels of circulating MDSCs (but not Tregs) and tumor grade. CyTOF analyses revealed that glioblastoma (GBM, grade IV) patients with a favorable prognosis had a decrease in systemic MDSC and immunosuppressive NK2 cell populations and an increase in DCs over time, while the reverse was observed in patients with poor prognosis. High levels of intratumoral MDSCs upon recurrence correlated with reduced overall survival in GBM patients.
Glioblastoma (GBM) remains uniformly lethal, and despite a large accumulation of immune cells in the microenvironment, there is limited antitumor immune response. To overcome these challenges, a comprehensive understanding of GBM systemic immune response during disease progression is required. Here, we integrated multiparameter flow cytometry and mass cytometry TOF (CyTOF) analysis of patient blood to determine changes in the immune system among tumor types and over disease progression. Utilizing flow cytometry analysis in a cohort of 259 patients ranging from benign to malignant primary and metastatic brain tumors, we found that GBM patients had a significant elevation in myeloid-derived suppressor cells (MDSCs) in peripheral blood but not immunosuppressive Tregs. In GBM patient tissue, we found that increased MDSC levels in recurrent GBM portended poor prognosis. CyTOF analysis of peripheral blood from newly diagnosed GBM patients revealed that reduced MDSCs over time were accompanied by a concomitant increase in DCs. GBM patients with extended survival also had reduced MDSCs, similar to the levels of low-grade glioma (LGG) patients. Our findings provide a rationale for developing strategies to target MDSCs, which are elevated in GBM patients and predict poor prognosis.
Author Info: (1) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. Department of Molecular Medicine, Cleveland Clinic Lerner Coll
Author Info: (1) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case, Western Reserve University, Cleveland, Ohio, USA. (2) Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience, UCLA, USA. (3) Department of Pathology, Odense University Hospital, Odense, Denmark. Department of Clinical Research, University of Southern Denmark, Odense, Denmark. (4) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. (5) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case, Western Reserve University, Cleveland, Ohio, USA. (6) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. (7) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. (8) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. (9) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. (10) Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience, UCLA, USA. Department of Biophysics and Center of Biotechnology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS-Brazil. (11) Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and. (12) Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and. (13) Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and. Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA. (14) Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case, Western Reserve University, Cleveland, Ohio, USA. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and. (15) Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and. Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA. (16) Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. (17) Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience, UCLA, USA. (18) Department of Pathology, Odense University Hospital, Odense, Denmark. Department of Clinical Research, University of Southern Denmark, Odense, Denmark. (19) Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case, Western Reserve University, Cleveland, Ohio, USA. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and. Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA. Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA. (20) Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case, Western Reserve University, Cleveland, Ohio, USA. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and. Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.
