title: Glioma grade is associated with the accumulation and activity of cells bearing M2 monocyte markers.
abstract: OBJECTIVE
  This study is directed at identifying the cell source(s) of immunomodulatory cytokines in high-grade gliomas and establishing whether the analysis of associated markers has implications for tumor grading.
  
  
  METHODS
  Glioma specimens classified as WHO grade II-IV by histopathology were assessed by gene expression analysis and immunohistochemistry to identify the cells producing interleukin (IL)-10, which was confirmed by flow cytometry and factor secretion in culture. Finally, principal component analysis (PCA) and mixture discriminant analysis (MDA) were used to investigate associations between expressed genes and glioma grade.
  
  
  RESULTS
  The principle source of glioma-associated IL-10 is a cell type that bears phenotype markers consistent with M2 monocytes but does not express all M2-associated genes. Measures of expression of the M2 cell markers CD14, CD68, CD163, and CD204, which are elevated in high-grade gliomas, and the neutrophil/myeloid-derived suppressor cell (MDSC) subset marker CD15, which is reduced, provide the best index of glioma grade.
  
  
  CONCLUSIONS
  Grade II and IV astrocytomas can be clearly differentiated on the basis of the expression of certain M2 markers in tumor tissues, whereas grade III astrocytomas exhibit a range of expression between the lower and higher grade specimens. The content of CD163(+) cells distinguishes grade III astrocytoma subsets with different prognosis.
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Prosniak
authors.forename: Larry A
authors.initials: LA
authors.lastname: Harshyne
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Kenyon
authors.forename: Kamila
authors.initials: K
authors.lastname: Bedelbaeva
authors.forename: Tatiyana V
authors.initials: TV
authors.lastname: Apanasovich
authors.forename: Ellen
authors.initials: E
authors.lastname: Heber-Katz
authors.forename: Mark T
authors.initials: MT
authors.lastname: Curtis
authors.forename: Paolo
authors.initials: P
authors.lastname: Cotzia
authors.forename: D Craig
authors.initials: DC
authors.lastname: Hooper
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005909:Glioblastoma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; C508609:IL10 protein, human; D007155:Immunologic Factors; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D016753:Interleukin-10