Thiel Annette, Pries Ralph, Jeske Sabrina, Trenkle Thomas, Wollenberg Barbara
Department of Otorhinolaryngology, University of Schleswig-Holstein Campus Lübeck, 23538 Lübeck, Germany.
Anticancer Res. 2009 Aug;29(8):3019-25.
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.
浸润头颈部鳞状细胞癌(HNSCC)实体瘤组织及引流淋巴结的浆细胞样树突状细胞(PDC)表现出免疫反应受损。HNSCC分泌的免疫抑制细胞因子已被认为是导致α干扰素(IFN-α)产生减少的原因,而其对PDC迁移的影响尚未得到研究。
通过磁珠分离从人外周血中分离出PDC。使用流式细胞术、迁移试验和酶联免疫吸附测定(ELISA)技术分析细胞功能和特性。
我们发现HNSCC和CpG寡核苷酸对PDC的迁移和IFN-α产生有相反的影响。此外,我们证明HNSCC诱导的向基质细胞衍生因子-1(SDF-1)和巨噬细胞炎性蛋白1β(MIP-1β)的迁移不依赖于趋化因子(CXC基序)受体4(CXCR4)和趋化因子(C-C基序)受体5(CCR5)的表面密度。
我们提出,HNSCC触发的PDC迁移很可能与受肿瘤微环境影响强烈调节的多水平过程有关。