PMID- 19609241
OWN - NLM
STAT- MEDLINE
DCOM- 20091008
LR  - 20220224
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
VI  - 32
IP  - 5
DP  - 2009 Jun
TI  - Ovarian cancer-derived glycodelin impairs in vitro dendritic cell maturation.
PG  - 492-7
LID - 10.1097/CJI.0b013e3181a59fa9 [doi]
AB  - Local immunosuppressive mechanisms shape the tumor microenvironment and 
      contribute to carcinogenesis. In ovarian cancer such mechanisms have been shown 
      to influence survival. Dendritic cells (DCs) are central immunity regulators and 
      induce potent cytotoxic T-cell responses as well as peripheral tolerance 
      depending on modulatory stimuli. Here, we show that ovarian cancer-derived 
      glycodelin (Gd), a glycoprotein that physiologically modulates local immunity in 
      early pregnancy, induces a tolerogenic DC phenotype. Gd was isolated with high 
      performance liquid chromatography from the malignant ascites of ovarian cancer 
      patients. DCs were generated from monocytes of healthy donors and exposed to Gd 
      with or without an inflammatory stimulus (tumor necrosis factor-alpha and 
      interleukin 1-beta). We investigated the effect of Gd on DC surface marker 
      expression, endopinocytotic activity, cytokine profile, and lymphoproliferative 
      activity. DCs that were exposed to Gd altered their phenotype as seen by a 
      differential expression of costimulatory molecules, whereas expression of 
      DC-specific intercellular adhesion molecule 3-grabbing nonintegrin, a marker of 
      an immature phenotype, was increased. Functional data provided further evidence 
      for the immature/tolerogenic properties of Gd-pretreated DCs. Antigen uptake was 
      retained, production of interleukin-10 was increased, and lymphoproliferative 
      activity was reduced. This effect was reversible by adding Gd-blocking 
      antibodies. Gd, which is found in the malignant ascites of ovarian cancer 
      patients, induces a tolerogenic phenotype in DC, thereby shaping an 
      immunodeficient tumor micromilieu.
FAU - Scholz, Christoph
AU  - Scholz C
AD  - Department of Obstetrics and Gynecology, Ludwig-Maximilians University, 
      Innenstadt, Munich, Germany. cscholz@med.lmu.de
FAU - Rampf, Elisabeth
AU  - Rampf E
FAU - Toth, Bettina
AU  - Toth B
FAU - Brunnhuber, Regina
AU  - Brunnhuber R
FAU - Weissenbacher, Tobias
AU  - Weissenbacher T
FAU - Friese, Klaus
AU  - Friese K
FAU - Jeschke, Udo
AU  - Jeschke U
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Glycodelin)
RN  - 0 (Glycoproteins)
RN  - 0 (ICAM3 protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (PAEP protein, human)
RN  - 0 (Pregnancy Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Antigen Presentation
MH  - Antigens, CD/genetics/immunology/metabolism
MH  - Antigens, Differentiation/genetics/immunology/metabolism
MH  - Antigens, Neoplasm/immunology/isolation & purification/metabolism
MH  - Cell Adhesion Molecules/genetics/immunology/metabolism
MH  - Cell Differentiation/drug effects/immunology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - Dendritic Cells/drug effects/*immunology/metabolism/pathology
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glycodelin
MH  - Glycoproteins/*immunology/isolation & purification/*metabolism/pharmacology
MH  - Humans
MH  - Immune Tolerance
MH  - Immunosuppressive Agents/immunology/metabolism/pharmacology
MH  - Interferon-beta/metabolism
MH  - Interleukin-10/genetics/immunology/metabolism
MH  - Leukocytes, Mononuclear/pathology
MH  - Ovarian Neoplasms/genetics/immunology/*metabolism/pathology
MH  - Pregnancy
MH  - Pregnancy Proteins/*immunology/isolation & purification/*metabolism/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2009/07/18 09:00
MHDA- 2009/10/09 06:00
CRDT- 2009/07/18 09:00
PHST- 2009/07/18 09:00 [entrez]
PHST- 2009/07/18 09:00 [pubmed]
PHST- 2009/10/09 06:00 [medline]
AID - 00002371-200906000-00007 [pii]
AID - 10.1097/CJI.0b013e3181a59fa9 [doi]
PST - ppublish
SO  - J Immunother. 2009 Jun;32(5):492-7. doi: 10.1097/CJI.0b013e3181a59fa9.