PMID- 20179016
OWN - NLM
STAT- MEDLINE
DCOM- 20120827
LR  - 20220409
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 12
IP  - 7
DP  - 2010 Jul
TI  - Systemic immune suppression in glioblastoma: the interplay between 
      CD14+HLA-DRlo/neg monocytes, tumor factors, and dexamethasone.
PG  - 631-44
LID - 10.1093/neuonc/noq001 [doi]
AB  - Patients with glioblastoma (GBM) exhibit profound systemic immune defects that 
      affect the success of conventional and immune-based treatments. A better 
      understanding of the contribution of the tumor and/or therapy on systemic immune 
      suppression is necessary for improved therapies, to monitor negative effects of 
      novel treatments, to improve patient outcomes, and to increase understanding of 
      this complex system. To characterize the immune profile of GBM patients, we 
      phenotyped peripheral blood and compared these to normal donors. In doing so, we 
      identified changes in systemic immunity associated with both the tumor and 
      dexamethasone treated tumor bearing patients. In particular, dexamethasone 
      exacerbated tumor associated lymphopenia primarily in the T cell compartment. We 
      have also identified unique tumor and dexamethasone dependent altered monocyte 
      phenotypes. The major population of altered monocytes (CD14(+)HLA-DR(lo/neg)) had 
      a phenotype distinct from classical myeloid suppressor cells. These cells 
      inhibited T cell proliferation, were unable to fully differentiate into mature 
      dendritic cells, were associated with dexamethasone-mediated changes in CCL2 
      levels, and could be re-created in vitro using tumor supernatants. We provide 
      evidence that tumors express high levels of CCL2, can contain high numbers of 
      CD14(+) cells, that tumor supernatants can transform CD14(+)HLA-DR(+) cells into 
      CD14(+)HLA-DR(lo/neg) immune suppressors, and that dexamethasone reduces CCL2 in 
      vitro and is correlated with reduction of CCL2 in vivo. Consequently, we have 
      developed a model for tumor mediated systemic immune suppression via recruitment 
      and transformation of CD14(+) cells.
FAU - Gustafson, Michael P
AU  - Gustafson MP
AD  - Division of Transfusion Medicine, Mayo Clinic, 200 1st St. SW, Rochester, MN 
      55905, USA.
FAU - Lin, Yi
AU  - Lin Y
FAU - New, Kent C
AU  - New KC
FAU - Bulur, Peggy A
AU  - Bulur PA
FAU - O'Neill, Brian Patrick
AU  - O'Neill BP
FAU - Gastineau, Dennis A
AU  - Gastineau DA
FAU - Dietz, Allan B
AU  - Dietz AB
LA  - eng
GR  - P50 CA 108961/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100223
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Biomarkers, Tumor/immunology/metabolism
MH  - Cell Communication/genetics/*immunology
MH  - Cells, Cultured
MH  - Dexamethasone/*metabolism/pharmacology
MH  - Glioblastoma/drug therapy/genetics/*immunology
MH  - HLA-DR Antigens/*metabolism
MH  - Humans
MH  - *Immune Tolerance/drug effects/immunology
MH  - Lipopolysaccharide Receptors/*biosynthesis/genetics
MH  - Monocytes/drug effects/*immunology/pathology
PMC - PMC2940665
EDAT- 2010/02/25 06:00
MHDA- 2012/08/28 06:00
PMCR- 2011/07/01
CRDT- 2010/02/25 06:00
PHST- 2010/02/25 06:00 [entrez]
PHST- 2010/02/25 06:00 [pubmed]
PHST- 2012/08/28 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - noq001 [pii]
AID - 10.1093/neuonc/noq001 [doi]
PST - ppublish
SO  - Neuro Oncol. 2010 Jul;12(7):631-44. doi: 10.1093/neuonc/noq001. Epub 2010 Feb 23.