Ormandy Lars-A, Farber Anatol, Cantz Tobias, Petrykowska Susanne, Wedemeyer Heiner, Horning Monique, Lehner Frank, Manns Michael-P, Korangy Firouzeh, Greten Tim-F
Department of Gastroenterology, Hepatology und Endocrinology, Medizinische Hochschule Hannover, Carl Neuberg Str. 1, 30625 Hannover, Germany.
World J Gastroenterol. 2006 May 28;12(20):3275-82. doi: 10.3748/wjg.v12.i20.3275.
To analyze the phenotype and function of dendritic cells (DC) from patients with hepatocellular carcinoma (HCC) in order to understand their role in this disease.
Myeloid dendritic cells were enumerated in peripheral blood of HCC patients. CD80, CD83, CD86 and HLA-DR expression on naive and stimulated myeloid dendritic cells from peripheral blood were analyzed. Myeloid dendritic cells were isolated from peripheral blood and their function was tested. Phagocytosis was analyzed using FITC-dextran beads, peptide specific stimulation, the capacity to stimulate allogeneic T cells and secretion of cytokines upon poly dI:dC was tested.
Myeloid dendritic cells were reduced in patients with HCC. No differences in CD80, CD83, CD86 and HLA-DR expression were found on naive and stimulated myeloid dendritic cells from HCC patients and healthy controls. Normal phagocytosis or stimulation of peptide specific T cells was observed in contrast to an impaired allo-stimulatory capacity and a reduced IL-12 secretion.
Impaired IL-12 production of mDCs in patients could lead to an impaired stimulatory capacity of naive T cells suggesting that IL-12 directed therapies may enhance tumor specific immune responses in HCC patients.
分析肝细胞癌(HCC)患者树突状细胞(DC)的表型和功能,以了解其在该疾病中的作用。
对HCC患者外周血中的髓样树突状细胞进行计数。分析外周血中未成熟和经刺激的髓样树突状细胞上CD80、CD83、CD86和HLA-DR的表达。从外周血中分离髓样树突状细胞并检测其功能。使用异硫氰酸荧光素标记的葡聚糖珠分析吞噬作用,测试肽特异性刺激、刺激同种异体T细胞的能力以及聚肌苷酸:聚胞苷酸刺激后细胞因子的分泌。
HCC患者的髓样树突状细胞减少。HCC患者和健康对照者未成熟和经刺激的髓样树突状细胞上CD80、CD83、CD86和HLA-DR的表达没有差异。观察到正常的吞噬作用或肽特异性T细胞的刺激,而异种异体刺激能力受损且白细胞介素-12分泌减少。
患者髓样树突状细胞白细胞介素-12产生受损可能导致未成熟T细胞刺激能力受损,提示白细胞介素-12导向疗法可能增强HCC患者的肿瘤特异性免疫反应。