Kapka-Skrzypczak Lucyna, Wolinska Ewa, Szparecki Grzegorz, Czajka Magdalena, Skrzypczak Maciej
Department of Medical Biology and Translational Research, University of Information Technology and Management, Faculty of Medicine, Rzeszow, Poland ; Department of Molecular Biology and Translational Research, Institute of Rural Health, Lublin, Poland.
Department of Pathology, Medical University of Warsaw, Warsaw, Poland.
Cent Eur J Immunol. 2015;40(3):349-53. doi: 10.5114/ceji.2015.54598. Epub 2015 Oct 15.
One of the potential therapeutic methods of cancer treatment is the immunotherapy with monoclonal antibodies. This kind of therapy, although devoid of serious side effects, has often insufficient efficacy. The presence of complement inhibitors on the cancer cells, which are able to inactivate complement-mediated immune response represents one of the main reasons for the inefficiency of such therapy. In our studies we investigated the expression of main membrane-bound and fluid-phase complement regulators: CD55, CD59 and factor H/factor H-like in tumour samples of ovarian and corpus uteri cancer. Tissue samples were collected from 50 patients and stained immunohistochemically, with the use of peroxidase-based immunodetection system. Immunohistochemical analysis revealed that complement inhibitors are present in examined tumors although their presence is heterogenous. The most prevalent is the presence of factor H/H-like, localized mostly in tumor stroma and within vascular structures. Membrane bound complement inhibitors are less prominently expressed by cancer cells. CD55 was detected in low percentage of cells, predominantly within cancer tubules. CD59 immunoreactivity was more prevalent in cancer cells, and was localized particularly at the margin of cancer cell tubules. Our results demonstrate that the most prominent complement inhibitor in cancer of ovary and corpus uteri origin is factor H/factor H-like. Blocking or downregulation of this inhibitor should be taken into consideration with regards to improving the efficiency of immunotherapy with monoclonal antibodies.
癌症治疗的潜在方法之一是单克隆抗体免疫疗法。这种疗法虽然没有严重的副作用,但疗效往往不足。癌细胞上存在补体抑制剂,能够使补体介导的免疫反应失活,这是这种疗法效率低下的主要原因之一。在我们的研究中,我们调查了卵巢癌和子宫体癌肿瘤样本中主要的膜结合型和液相补体调节因子:CD55、CD59以及因子H/类因子H的表达情况。从50名患者身上采集组织样本,并使用基于过氧化物酶的免疫检测系统进行免疫组织化学染色。免疫组织化学分析显示,在所检查的肿瘤中存在补体抑制剂,尽管其存在是异质性的。最普遍存在的是因子H/类因子H,主要定位于肿瘤基质和血管结构内。膜结合型补体抑制剂在癌细胞中的表达不太明显。CD55在低比例的细胞中被检测到,主要在癌小管内。CD59免疫反应性在癌细胞中更普遍,尤其定位于癌细胞小管的边缘。我们的结果表明,卵巢和子宫体来源的癌症中最突出的补体抑制剂是因子H/类因子H。考虑到提高单克隆抗体免疫疗法的效率,应该考虑阻断或下调这种抑制剂。