title: Expression of iNOS, CD163 and ARG-1 taken as M1 and M2 markers of microglial polarization in human glioblastoma and the surrounding normal parenchyma.
abstract: Microglia and macrophages appear to be the most common cells in the GBM microenvironment. In the present study we investigated the status of macrophages/microglia activation in surgical specimens from 41 patients diagnosed with grade IV GBM. For each patient we analyzed both the center of tumor and the parenchyma surrounding the tumor. The specimens were stained for: i) IBA1, a 17-kDa EF hand protein specifically expressed in microglia/macrophages ii) CD163, a cell surface antigen associated with M2 phenotype; iii) iNOS, taken as a functional marker of M1 phenotype, and iv) ARG-I, taken as a functional marker of M2 phenotype. Staining was scored in a double-blinded score on a scale from 0 to 5. Our results suggest that CD163 expression is higher within the tumor than in surrounding periphery in both male and female patients; while iNOS is higher within the tumor in males, no significant difference was found for ARG-1. In addition, analyzing the data in TGCA database, we found that CD163 expression was significantly and inversely correlated with mean survival times, with average survival times ranging from 448days in patients having low expression, to 319 in mid, and 353 in patients with high CD163 expressing tumors. In contrast, no significant association was found between survival time and ARG-1 or iNOS expression.
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F. Vito 1, Rome, 00168, Italy. Electronic address: lucia.lisi@unicatt.it.
authors.forename: L
authors.initials: L
authors.lastname: Lisi
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F. Vito 1, Rome, 00168, Italy. Electronic address: gabriella.ciotti@hotmail.it.
authors.forename: G M P
authors.initials: GM
authors.lastname: Ciotti
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: brauny@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Braun
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: sergey@uic.edu.
authors.forename: S
authors.initials: S
authors.lastname: Kalinin
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F. Vito 1, Rome, 00168, Italy. Electronic address: diego.curro@unicatt.it.
authors.forename: D
authors.initials: D
authors.lastname: Currò
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F. Vito 1, Rome, 00168, Italy. Electronic address: cinzia.dellorusso@unicatt.it.
authors.forename: C
authors.initials: C
authors.lastname: Dello Russo
authors.affiliation: Institute of Pathology, Catholic University Medical School, Rome, Italy. Electronic address: antonella.coli@rm.unicatt.it.
authors.forename: A
authors.initials: A
authors.lastname: Coli
authors.affiliation: Institute of Neurosurgery, Catholic University Medical School, Rome, Italy. Electronic address: amangiola@rm.unicatt.it.
authors.forename: A
authors.initials: A
authors.lastname: Mangiola
authors.affiliation: Institute of Neurosurgery, Catholic University Medical School, Rome, Italy. Electronic address: anilec@rm.unicatt.it.
authors.forename: C
authors.initials: C
authors.lastname: Anile
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA; Department of Veterans Affairs, Jesse Brown VA Medical Center, Chicago, IL, USA. Electronic address: dlfeins@uic.edu.
authors.forename: D L
authors.initials: DL
authors.lastname: Feinstein
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F. Vito 1, Rome, 00168, Italy. Electronic address: pierluigi.navarra@unicatt.it.
authors.forename: P
authors.initials: P
authors.lastname: Navarra
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001119:Arginase / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D016764:Cell Polarity; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D017628:Microglia / Q000502:physiology*; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D000072356:Parenchymal Tissue / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016019:Survival Analysis; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D001119:Arginase
keywords: ARG-I; CD163; Glioblastoma; M1 polarization; M2 polarization; Microglia; Periphery; Tumor; iNOS