| First Author | Zhou Z | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 11 | Pages | e78618 |
| PubMed ID | 24236027 | Mgi Jnum | J:209210 |
| Mgi Id | MGI:5566713 | Doi | 10.1371/journal.pone.0078618 |
| Citation | Zhou Z, et al. (2013) Growth differentiation factor-15 suppresses maturation and function of dendritic cells and inhibits tumor-specific immune response. PLoS One 8(11):e78618 |
| abstractText | 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-beta1 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. |
