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Updated: May 5, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Growth differentiation factor-15 suppresses maturation and function of dendritic cells and inhibits tumor-specific
Zhizhong Zhou1, Weina Li, Yang Song
1The State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi, China ; Department of Biopharmaceutics, Fourth Military Medical University, Xi'an, Shaanxi, China.
Abstract:
Dendritic cells (DCs) play a key role in the initiation stage of an antigen-specific immune response. A variety of tumor-derived factors (TDFs) can suppress DC maturation and function, resulting in defects in the tumor-specific immune response. To identify unknown TDFs that may suppress DCs maturation and function, we established a high-throughput screening technology based on a human liver tumor T7 phage cDNA library and screened all of the proteins derived from hepatoma cells that potentially interact with immature DCs. Growth/differentiation factor-15 (GDF-15) was detected and chosen for further study. By incubation of DCs cultures with GDF-15, we demonstrate that GDF-15 can inhibit surface protrusion formation during DC maturation; suppress the membrane expression of CD83, CD86 and HLA-DR on DCs; enhance phagocytosis by DCs; reduce IL-12 and elevate TGF-β1 secretion by DCs; inhibit T cell stimulation and cytotoxic T lymphocyte (CTL) activation by DCs. By building tumor-bearing mouse models, we demonstrate that GDF-15 can inhibit the ability of DCs to stimulate a tumor-specific immune response in vivo. These results indicate that GDF-15 may be one of the critical molecules that inhibit DC maturation and function and are involved in tumor immune escape. Thus, GDF-15 may be a novel target in tumor immunotherapy.
Insights
Growth/differentiation factor-15 (GDF-15) suppresses dendritic cell (DC) maturation and function, hindering anti-tumor immunity. This molecule may be a novel target for tumor immunotherapy.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Dendritic cells (DCs) are crucial for initiating antigen-specific immune responses.
- Tumor-derived factors (TDFs) can impair DC function, leading to immune evasion.
- Identifying novel TDFs is essential for developing effective cancer immunotherapies.
Purpose of the Study:
- To identify novel tumor-derived factors that suppress dendritic cell (DC) maturation and function.
- To investigate the role of Growth/differentiation factor-15 (GDF-15) in modulating DC activity and anti-tumor immunity.
Main Methods:
- High-throughput screening using a human liver tumor T7 phage cDNA library to identify TDFs interacting with immature DCs.
- In vitro experiments culturing DCs with GDF-15 to assess its effects on DC maturation markers, phagocytosis, cytokine secretion, and T cell stimulation.
- In vivo studies using tumor-bearing mouse models to evaluate GDF-15's impact on DC-mediated anti-tumor immune responses.
Main Results:
- Growth/differentiation factor-15 (GDF-15) was identified as a TDF that inhibits DC maturation, evidenced by reduced expression of CD83, CD86, and HLA-DR.
- GDF-15 suppressed IL-12 secretion while increasing TGF-β1 production by DCs, impairing T cell stimulation and cytotoxic T lymphocyte (CTL) activation.
- In vivo, GDF-15 inhibited the capacity of DCs to elicit a tumor-specific immune response.
Conclusions:
- GDF-15 is a key molecule that suppresses dendritic cell (DC) maturation and function, contributing to tumor immune escape.
- GDF-15 represents a potential novel therapeutic target for enhancing anti-tumor immunity in cancer immunotherapy.
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