Kúdela P, Schwarczová Z, Sedlák J, Bizik J
Department of Tumor Cell Biology, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Neoplasma. 2001;48(5):382-8.
Progressive tumor proliferation may be associated with suppression of the immune response. Several different mechanisms can contribute to immune evasion. It is generally proposed that inhibition of dendritic cell functions would be a key mechanism by which tumors could escape immune surveillance. Therefore, the purpose of this study was to evaluate the capacity of HeLa cells conditioned medium (HeLa-CM) to modulate phenotypic and functional parameters of human peripheral blood monocyte-derived dendritic cells (DCs). Two types of reference DCs population were generated in vitro, the first cultured in the presence of IL-4 and GM-CSF which represented immature DCs (iDCs) and the second, representing mature DCs (mDCs), was raised from the iDCs by additional stimulation with a maturation cocktail - TNF-alpha, IL-1beta, IL-6, PGE2. In parallel, the iDCs were treated with HeLa-CM collected from the tumor cells. The analysis of DC populations demonstrated that the HeLa-CM prevented maturation of these cells and also impaired their capacity to uptake an antigen and stimulate proliferation of allogeneic T cells. In contrast, HeLa-CM modulated DCs exhibited a 3-fold increase mobility over iDCs. The latter functional capacity did not correlate with the levels of matrix metalloproteinase expression in the analysed cells. Altogether, our results provide evidence that HeLa cells produce soluble factors that might dramatically alter basic phenotypic and functional characteristics of DCs.
肿瘤的进行性增殖可能与免疫反应的抑制有关。几种不同的机制可导致免疫逃逸。一般认为,抑制树突状细胞功能是肿瘤逃避免疫监视的关键机制。因此,本研究的目的是评估人乳头瘤病毒18型(HeLa)细胞条件培养基(HeLa-CM)调节人外周血单核细胞来源的树突状细胞(DCs)表型和功能参数的能力。在体外产生了两种类型的参考DC群体,第一种在白细胞介素-4(IL-4)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)存在下培养,代表未成熟DC(iDCs),第二种代表成熟DC(mDCs),是通过用成熟鸡尾酒(肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、前列腺素E2(PGE2))额外刺激从iDCs培养而来。同时,用从肿瘤细胞收集的HeLa-CM处理iDCs。对DC群体的分析表明,HeLa-CM阻止了这些细胞的成熟,还损害了它们摄取抗原和刺激同种异体T细胞增殖的能力。相比之下,经HeLa-CM调节的DCs比iDCs表现出高三倍的迁移率。后一种功能能力与分析细胞中基质金属蛋白酶的表达水平无关。总之,我们的结果提供了证据,表明HeLa细胞产生的可溶性因子可能会显著改变DCs的基本表型和功能特征。