PMID- 20308313
OWN - NLM
STAT- MEDLINE
DCOM- 20100708
LR  - 20211203
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 12
IP  - 4
DP  - 2010 Apr
TI  - Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor 
      cell-like properties.
PG  - 351-65
LID - 10.1093/neuonc/nop023 [doi]
AB  - Glioblastoma patients are immunosuppressed, yet glioblastomas are highly 
      infiltrated by monocytes/macrophages. Myeloid-derived suppressor cells (MDSC; 
      immunosuppressive myeloid cells including monocytes) have been identified in 
      other cancers and correlate with tumor burden. We hypothesized that glioblastoma 
      exposure causes normal monocytes to assume an MDSC-like phenotype and that MDSC 
      are increased in glioblastoma patients. Healthy donor human CD14(+) monocytes 
      were cultured with human glioblastoma cell lines. Controls were cultured alone or 
      with normal human astrocytes. After 48 hours, glioblastoma-conditioned monocytes 
      (GCM) were purified using magnetic beads. GCM cytokine and costimulatory 
      molecular expression, phagocytic ability, and ability to induce apoptosis in 
      activated lymphocytes were assessed. The frequency of MDSC was assessed by flow 
      cytometry in glioma patients' blood and in GCM in vitro. As predicted, GCM have 
      immunosuppressive, MDSC-like features, including reduced CD14 (but not CD11b) 
      expression, increased immunosuppressive interleukin-10, transforming growth 
      factor-beta, and B7-H1 expression, decreased phagocytic ability, and increased 
      ability to induce apoptosis in activated lymphocytes. Direct contact between 
      monocytes and glioblastoma cells is necessary for complete induction of these 
      effects. In keeping with our hypothesis, glioblastoma patients have increased 
      circulating MDSC compared with normal donors and MDSC are increased in 
      glioma-conditioned monocytes in vitro. To our knowledge, this has not been 
      reported previously. Although further study is needed to directly characterize 
      their origin and function in glioblastoma patients, these results suggest that 
      MDSC may be an important contributor to systemic immunosuppression and can be 
      modeled in vitro by GCM.
FAU - Rodrigues, Jennifer C
AU  - Rodrigues JC
AD  - Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, 
      Minnesota 55905, USA.
FAU - Gonzalez, Guido C
AU  - Gonzalez GC
FAU - Zhang, Lei
AU  - Zhang L
FAU - Ibrahim, George
AU  - Ibrahim G
FAU - Kelly, John J
AU  - Kelly JJ
FAU - Gustafson, Michael P
AU  - Gustafson MP
FAU - Lin, Yi
AU  - Lin Y
FAU - Dietz, Allan B
AU  - Dietz AB
FAU - Forsyth, Peter A
AU  - Forsyth PA
FAU - Yong, V Wee
AU  - Yong VW
FAU - Parney, Ian F
AU  - Parney IF
LA  - eng
GR  - P50 CA108961/CA/NCI NIH HHS/United States
GR  - CA108961-05/CA/NCI NIH HHS/United States
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091222
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (CD11b Antigen)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharide Receptors)
SB  - IM
CIN - Neuro Oncol. 2010 Apr;12(4):319. PMID: 20308309
MH  - Apoptosis
MH  - Brain Neoplasms/metabolism/*pathology
MH  - CD11b Antigen/metabolism
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Culture Media, Conditioned/pharmacology
MH  - Cytokines/metabolism
MH  - Flow Cytometry
MH  - Glioblastoma/metabolism/*pathology
MH  - Humans
MH  - Immunosuppression Therapy
MH  - Leukocytes, Mononuclear/metabolism/*pathology
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Monocytes/metabolism/*pathology
MH  - Myeloid Cells/metabolism/*pathology
PMC - PMC2940603
EDAT- 2010/03/24 06:00
MHDA- 2010/07/09 06:00
PMCR- 2011/04/01
CRDT- 2010/03/24 06:00
PHST- 2010/03/24 06:00 [entrez]
PHST- 2010/03/24 06:00 [pubmed]
PHST- 2010/07/09 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - nop023 [pii]
AID - 10.1093/neuonc/nop023 [doi]
PST - ppublish
SO  - Neuro Oncol. 2010 Apr;12(4):351-65. doi: 10.1093/neuonc/nop023. Epub 2009 Dec 22.