Defective receptor expression and dendritic cell differentiation of monocytes in glioblastomas.
OBJECTIVE
Better characterization of the changes that occur in the circulating monocytes of patients with glioblastoma has become more important recently as monocyte-derived dendritic cells are used as adjuvants in the development of glioma vaccines. This study seeks to develop understanding of the phenotypic changes that occur in circulating monocytes of patients with intracranial cancer and to assess the ability of these cells to differentiate into mature dendritic cells.


METHODS
Monocyte expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1, TNFRII, and GMCSFR were compared between three cohorts: patients with intracranial glioblastoma (n = 15), patients with intracranial metastases (n = 9), and a group of healthy controls (n = 10). Monocytes were then tested for their ability to differentiate into mature dentritic cells based on morphology, CD83 expression and high levels of co-stimulatory molecules.


RESULTS
Comprehensive analysis of monocyte receptor expression demonstrated significantly reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients with glioblastoma but not in patients with intracranial metastases compared with a group of healthy controls. GMCSFR expression was significantly reduced in both patients with glioblastoma and intracranial metastases. Additionally, the monocytes of patients with glioblastoma showed a reduced capacity to differentiate into mature dendritic cells as identified by CD83 expression, receptor expression, and morphology.


CONCLUSIONS
Peripheral monocytes are phenotypically altered in the setting of glioblastoma and display a reduced functional capacity to differentiate into mature dendritic cells.
Ogden
Alfred T
AT
Department of Neurological Surgery, The Neurological Institute, Columbia University, New York, New York 10032, USA. ato2@columbia.edu
Horgan
David
D
Waziri
Allen
A
Anderson
David
D
Louca
Joseph
J
McKhann
Guy M
GM
Sisti
Michael B
MB
Parsa
Andrew T
AT
Bruce
Jeffrey N
JN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D002454:Cell Differentiation; D002478:Cells, Cultured; D015331:Cohort Studies; D003713:Dendritic Cells / Q000473:pathology*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D006680:HLA Antigens; D007136:Immunoglobulins; D018799:Intercellular Adhesion Molecule-1; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D047889:Receptors, Tumor Necrosis Factor, Type II; D000097802:CD83 Antigen