Defective antitumor function of monocyte-derived macrophages from epithelial ovarian cancer patients
Defective antitumor function of monocyte-derived macrophages from epithelial ovarian cancer patients
复制标题
DOI：
10.1158/1078-0432.ccr-05-2254
复制
发表时间：
2006-03-01
影响因子：
11.5
通讯作者：
Freedman, RS
中科院分区：
文献类型：
--
作者：
Gordon, IO;Freedman, RS
目的：单核细胞/巨噬细胞（MO/MA）是一种重要但异质的免疫炎症细胞群体，具有不同的效应功能。我们检查并比较了上皮性卵巢癌患者外周血和腹水与正常供体外周血中的这些差异。比较了细胞表面亚群，细胞因子的产生，和CD 14（+）MO/MA和CD 14（亮）CD 16（-）HLA-DR+ MO/MA的FcR依赖性细胞毒性。正常供体外周血和上皮性卵巢癌患者外周血及腹水中的MA亚群。研究与巨噬细胞集落刺激因子和激活与脂多糖或脂多糖加重组IFN-γ的组合培养的单核细胞衍生的巨噬细胞进行了研究。结果：我们确定，MO/MA或其子集从上皮性卵巢癌患者的形态改变和显着减少抗体依赖性细胞介导的细胞毒性和吞噬活性比没有莫纳从正常供体。我们的研究结果还表明，上皮性卵巢癌患者和正常供体的单核细胞来源的巨噬细胞产生巨噬细胞集落刺激因子刺激的细胞因子，包括白细胞介素-8，肿瘤坏死因子-α和白细胞介素-6。这些发现首次强调了上皮性卵巢癌相关MO/MA的抗体依赖性细胞介导的细胞毒性和吞噬细胞功能缺陷，这可能对免疫生物学策略有影响。
Purpose: Monocytes/macrophages (MO/MA) are an important but heterogeneous population of immune inflammatory cells that have diverse effector functions. We examined and compared these differences in peripheral blood and ascites of epithelial ovarian cancer patients with peripheral blood of normal donors.Experimental Design: Comparisons were made of cell surface subsets, cytokine production, and FcR-dependent cytotoxicity of CD14(+) MO/MA and the CD14(bright) CD16(-)HLA-DR+ MO/MA subset in normal donor peripheral blood and peripheral blood and ascites from epithelial ovarian cancer patients. Studies were done on monocyte-derived macrophages cultured with macrophage colony-stimulating factor and activated with lipopolysaccharide or a combination of lipopolysaccharide plus recombinant IFN-gamma.Results: We determined that MO/MA or its subset from epithelial ovarian cancer patients had altered morphology and significantly less antibody-dependent cell-mediated cytotoxicity and phagocytic activity than did MONA from normal donors. Our findings also showed that monocyte-derived macrophages from both epithelial ovarian cancer patients and normal donors produce macrophage colony-stimulating factor-stimulated cytokines, including interleukin-8, tumor necrosis factor-alpha, and interleukin-6.Conclusions: These findings highlight for the first time the defective antibody-dependent cell-mediated cytotoxicity and phagocyte functions of epithelial ovarian cancer-associated MO/MA, which could have implications for immunobiotherapeutic strategies.