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Updated: Jun 21, 2026
In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells
Published on: February 18, 2015
Ovarian cancer-derived glycodelin impairs in vitro dendritic cell maturation
Christoph Scholz1, Elisabeth Rampf, Bettina Toth
1Department of Obstetrics and Gynecology, Ludwig-Maximilians University, Innenstadt, Munich, Germany. cscholz@med.lmu.de
Abstract:
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.
Insights
Ovarian cancer glycodelin (Gd) induces a tolerogenic dendritic cell (DC) phenotype, suppressing anti-tumor immunity. This glycodelin contributes to an immunodeficient tumor microenvironment, potentially impacting patient survival.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Local immunosuppressive mechanisms are crucial in shaping the tumor microenvironment and influencing cancer progression, particularly in ovarian cancer.
- Dendritic cells (DCs) are key immune regulators that can either promote anti-tumor cytotoxic T-cell responses or induce peripheral tolerance based on specific stimuli.
- Glycodelin (Gd), a glycoprotein known for its role in modulating immunity during pregnancy, is investigated for its impact on DCs in the context of ovarian cancer.
Purpose of the Study:
- To investigate the effect of ovarian cancer-derived glycodelin (Gd) on the phenotype and function of dendritic cells (DCs).
- To determine if Gd induces a tolerogenic DC phenotype that could contribute to immune suppression within the ovarian tumor microenvironment.
Main Methods:
- Glycodelin (Gd) was isolated from malignant ascites of ovarian cancer patients using high-performance liquid chromatography.
- Dendritic cells (DCs) were generated from healthy donor monocytes and treated with Gd, with or without inflammatory stimuli (TNF-alpha and IL-1-beta).
- Effects of Gd on DC surface marker expression, endopinocytosis, cytokine production (IL-10), and T-cell lymphoproliferative activity were assessed.
Main Results:
- Gd exposure altered DC surface marker expression, increasing DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (a marker of immaturity) and affecting costimulatory molecules.
- Gd-treated DCs exhibited characteristics of an immature and tolerogenic phenotype, including retained antigen uptake, increased IL-10 production, and reduced lymphoproliferative activity.
- The tolerogenic effect induced by Gd was reversible upon addition of Gd-blocking antibodies.
Conclusions:
- Ovarian cancer-derived glycodelin (Gd) induces a tolerogenic phenotype in dendritic cells (DCs).
- This Gd-induced tolerogenic DC phenotype contributes to shaping an immunodeficient tumor microenvironment in ovarian cancer.
- Gd's role in promoting immune tolerance may represent a mechanism influencing disease progression and survival in ovarian cancer patients.
