Growth Differentiation Factor-15 Suppresses Maturation and Function of Dendritic Cells and Inhibits Tumor-Specific Immune Response |
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| Authors: | Zhizhong Zhou Weina Li Yang Song Lili Wang Kuo Zhang Jing Yang Wei Zhang Haichuan Su Yingqi Zhang |
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| Institution: | 1. The State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi''an, Shaanxi, China.; 2. Department of Biopharmaceutics, Fourth Military Medical University, Xi''an, Shaanxi, China.; 3. Department of Oncology, Tangdu Hospital, Xi''an, Shaanxi, China.; 4. School of Life Sciences, Northwest University, Xi''an, Shaanxi, China.; Istituto Superiore di Sanità, Italy, |
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| 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. |
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