Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype

Konrad Gabrusiewicz, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Benjamin Rodriguez, Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Jun Wei, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Yuuri Hashimoto, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Luke M. Healy, Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Sourindra N. Maiti, Division of Pediatrics.
Ginu Thomas, Department of Diagnostic Radiology.
Shouhao Zhou, Department of Biostatistics.
Qianghu Wang, Department of Bioinformatics and Computational Biology.
Ahmed Elakkad, Department of Diagnostic Radiology.
Brandon D. Liebelt, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Nasser K. Yaghi, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ravesanker Ezhilarasan, Department of Radiation Oncology.
Neal Huang, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jeffrey S. Weinberg, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sujit S. Prabhu, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ganesh Rao, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Raymond Sawaya, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Lauren A. Langford, Department of Neuropathology.
Janet M. Bruner, Department of Neuropathology.
Gregory N. Fuller, Department of Neuropathology.
Amit Bar-Or, Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Wei Li, Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Rivka R. Colen, Department of Diagnostic Radiology.
Michael A. Curran, Department of Immunology, and.
Krishna P. Bhat, Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jack P. Antel, Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Laurence J. Cooper, Division of Pediatrics.
Erik P. Sulman, Department of Radiation Oncology.
Amy B. Heimberger, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Document Type

Article

Abstract

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.

Publication Date

1-1-2016

Publication Title

JCI insight

ISSN

2379-3708

Volume

1

Issue

2

PubMed ID

26973881

Digital Object Identifier (DOI)

10.1172/jci.insight.85841

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