Sakakura Koichi, Chikamatsu Kazuaki, Takahashi Katsumasa, Whiteside Theresa L, Furuya Nobuhiko
Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan.
Cancer Immunol Immunother. 2006 Feb;55(2):151-9. doi: 10.1007/s00262-005-0697-y. Epub 2005 May 12.
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.
树突状细胞(DCs)与T细胞之间的相互作用在免疫反应的调节和维持中起着关键作用。在癌症患者中,这些免疫细胞出现了各种免疫异常。在此,我们使用多色流式细胞术研究了头颈部鳞状细胞癌(SCCHN)患者外周血中DCs的比例和表型以及T细胞亚群的细胞因子谱。与健康供体相比,癌症患者髓样(CD11c(+))而非浆细胞样(CD123(+))DCs的百分比显著降低(P<0.05),并且总DCs和髓样DCs中HLA-DR的表达显著下降。对患者循环中T细胞亚群的同步分析显示,体外刺激后表达Th1和Th2细胞因子的CD4(+) T细胞比例显著增加,而Th1/Th2比值无任何偏差。髓样或总DCs上HLA-DR表达的相对水平与Th1/Th2比值呈正相关(P<0.01),循环DCs的总数与调节性CD4(+)CD25+(FoxP3+) T细胞的比例呈负相关(P<0.01)。这些结果表明,循环DCs比例的降低以及DCs中HLA-DR表达的下降可能对SCCHN患者的全身免疫反应产生重大影响。