title: Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype.
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.
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Gabrusiewicz
authors.affiliation: Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rodriguez
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Luke M
authors.initials: LM
authors.lastname: Healy
authors.affiliation: Division of Pediatrics.
authors.forename: Sourindra N
authors.initials: SN
authors.lastname: Maiti
authors.affiliation: Department of Diagnostic Radiology.
authors.forename: Ginu
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Department of Biostatistics.
authors.forename: Shouhao
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Bioinformatics and Computational Biology.
authors.forename: Qianghu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Diagnostic Radiology.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elakkad
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Liebelt
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nasser K
authors.initials: NK
authors.lastname: Yaghi
authors.affiliation: Department of Radiation Oncology.
authors.forename: Ravesanker
authors.initials: R
authors.lastname: Ezhilarasan
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weinberg
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sujit S
authors.initials: SS
authors.lastname: Prabhu
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Rao
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.affiliation: Department of Neuropathology.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Langford
authors.affiliation: Department of Neuropathology.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Bruner
authors.affiliation: Department of Neuropathology.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.affiliation: Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Diagnostic Radiology.
authors.forename: Rivka R
authors.initials: RR
authors.lastname: Colen
authors.affiliation: Department of Immunology, and.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Curran
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Bhat
authors.affiliation: Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel
authors.affiliation: Division of Pediatrics.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Cooper
authors.affiliation: Department of Radiation Oncology.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sulman
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger