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Maturation of circulating dendritic cells and imbalance of T-cell subsets in patients with squamous cell carcinoma of the head and neck
Authors:Koichi Sakakura  Kazuaki Chikamatsu  Katsumasa Takahashi  Theresa L Whiteside  Nobuhiko Furuya
Institution:(1) Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi 371-8511, Japan;(2) Departments of Pathology, Immunology and Otolaryngology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.27, 15213-1863 Pittsburgh, PA, USA
Abstract:Interactions between dendritic cells (DCs) and T cells play a pivotal role in the regulation and maintenance of immune responses. In cancer patients, various immunological abnormalities have been observed in these immune cells. Here, we investigated proportions and the phenotype of DCs and the cytokine profile of T-cell subsets in the peripheral blood of patients with squamous cell carcinoma of the head and neck (SCCHN), using multicolor flow cytometry. The percentage of myeloid (CD11c+), but not plasmacytoid (CD123+) DCs, was significantly lower (P<0.05) and expression of HLA-DR was significantly decreased in total and myeloid DCs of cancer patients compared to healthy donors. Simultaneous analyses of T-cell subsets in the patients’ circulation showed significantly increased proportions of CD4+ T cells expressing Th1 and Th2 cytokines after ex vivo stimulation without any skewing in the Th1/Th2 ratio. The relative level of HLA-DR expression on myeloid or total DCs positively correlated with the Th1/Th2 ratio (P<0.01), and the proportion of total circulating DCs was inversely correlated with that of regulatory CD4+CD25+ T cells (P<0.01). These results suggest that the decreased proportion of circulating DCs and decreased HLA-DR expression in DCs may have a major impact on systemic immune responses in patients with SCCHN.
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