Effect of head and neck cancer supernatant and CpG-oligonucleotides on migration and IFN-alpha production of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (PDCs) infiltrating solid tumor tissues and draining lymph nodes of head and neck squamous cell carcinoma (HNSCC) show an impaired immune response. Immunosuppressive cytokines secreted by HNSCC have been recognized to account for reduced interferon-alpha (IFN-alpha) production, whereas the influence on PDC migration has not yet been investigated. PDCs were isolated from human peripheral blood by magnetic bead separation. Cellular functions and characteristics were analyzed using flow cytometry, migration assays and ELISA techniques. We show that HNSCC and CpG oligonucleotides controversially influence the migration and IFN-alpha production of PDCs. Furthermore we demonstrate that HNSCC induced migration towards stromal cell-derived factor-1 (SDF-1) and macrophage inflammatory protein 1 beta (MIP-1beta) is not dependent upon the surface density of chemokine (CXC motif) receptor 4 (CXCR4) and chemokine (C-C motif) receptor 5 (CCR5). We propose that HNSCC triggered PDC migration is most likely linked to a multilevel process strongly modulated by tumor microenvironmental influences.