Artikel
Head and neck squamous cell carcinoma inhibit tumor-infiltrating plasmacytoid dendritic cells via TGF-ß
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Veröffentlicht: | 22. September 2005 |
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Gliederung
Text
Plasmacytoid dendritic cells (PDC) infiltrate tumor tissue of HNSCC. Immunostimulatory CpG oligodeoxynucleotides (CpG ODN) induce large amounts of IFN-α in PDC. Peritumoral administration of CpG ODN cures established tumors in mice (C26). Our earlier studies showed that tumor-infiltrating PDC are functionally impaired, but the mechanism leading to functional inhibition of PDC remained unknown. In the present study we sought to identify factors that contribute to this tumor-induced inhibition. We quantified the number of PDCs in single cell suspensions of HNSCC by flow cytometry. For functional analysis PDC were isolated from blood of healthy donors by MACS-BDCA-4 (magnetic activated cell sorting). For stimulation of PDC CpG ODN 2216 was used. Expression of TGF-β (transforming growth factor β), SDF-1 (stromal derived factor 1) und VEGF (vascular endothelial growth factor) was analysed in primary tumor tissue, tumor cell lines and in healthy mucosa by using real time PCR. We found that TGF-β was overexpressed in primary tumor tissue and tumor cell lines as compared to healthy mucosa. No significant changes were found for SDF-1 and VEGF. Recombinant TGF-β inhibited IFN-α production of PDC in vitro. Together these data demonstrate that TGF-β inhibits the Th1 bias of PDC which is important for an effective anti-tumor immune response. Future studies will show whether TGF-β is the only factor that contributes to tumor-mediated suppression of PDC function.