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.
Highlights
Dendritic cells (DCs), known as the most powerful professional antigen-presenting cells (APCs), initiate an antigen-specific immune response by the recognition, acquisition, processing and presentation of antigens to naıve resting T cells [1]
To identify unknown tumor-derived factors (TDFs) that may suppress DC 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 (iDCs)
These results indicated that phages that were capable of binding to iDCs were enriched
Summary
Dendritic cells (DCs), known as the most powerful professional antigen-presenting cells (APCs), initiate an antigen-specific immune response by the recognition, acquisition, processing and presentation of antigens to naıve resting T cells [1]. Phage display technology allows small peptides and protein libraries to be presented on the surface of filamentous phages and permits selection of specific peptides and proteins with high affinity. This technology has been used to identify peptides for species-specific recognition of peptides. Biopanning of phage-displayed peptide libraries on intact cells in culture and on the tissues has proven successful for isolating peptides that show high cell and tissue specificities This approach may be used to distinguish cancer cells from normal cells as well as to enable selective binding to different tumor types, even those with similar classifications [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
