Sievers Elisabeth, Dreimuller Patrick, Haferkamp Axel, Schmidt-Wolf Ingo G H, Buchler Markus W, Schmidt Jan, Marten Angela
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Urol Int. 2007;79(3):235-43. doi: 10.1159/000107956.
For a better understanding of the factors contributing to tumor progression in metastatic renal cell carcinoma and to identify possible targets for immunotherapeutic approaches, we characterized several primary cultures from renal cell carcinoma.
Cell cultures were tested for activity of telomerase, secretion of immunosuppressive cytokines and others. The induction of cytotoxic activity against the autologous tumor was tested in a cytotoxicity assay after coculture of immunological effector cells with antigen-pulsed dendritic cells. The data were tested for influence on survival.
We were able to establish primary cell cultures from 58 patients with renal cell carcinoma and their metastasis. 48/58 were positive for telomerase activity and all secreted IL-6, TGF-beta, VEGF and IL-8. High TGF-beta secretion, the activity of telomerase and the induction of a telomerase-specific immune response against telomerase peptides in telomerase-positive tumors had a significant impact on survival.
TGF-beta secretion, activity of telomerase in telomerase-positive tumors and the ability to generate a telomerase-specific immune response might serve as a prognostic marker for RCC. New approaches might focus on attacking the TGF-beta pathway and on induction of telomerase-specific immune cells.
为了更好地理解转移性肾细胞癌肿瘤进展的影响因素,并确定免疫治疗方法的可能靶点,我们对几种肾细胞癌原代培养物进行了特征分析。
对细胞培养物进行端粒酶活性、免疫抑制细胞因子分泌等检测。在免疫效应细胞与抗原脉冲树突状细胞共培养后,通过细胞毒性试验检测对自体肿瘤细胞毒性活性的诱导情况。对数据进行生存影响检测。
我们成功从58例肾细胞癌及其转移灶患者中建立了原代细胞培养物。58例中有48例端粒酶活性呈阳性,且均分泌白细胞介素-6(IL-6)、转化生长因子-β(TGF-β)、血管内皮生长因子(VEGF)和白细胞介素-8(IL-8)。高TGF-β分泌、端粒酶活性以及端粒酶阳性肿瘤中针对端粒酶肽的端粒酶特异性免疫反应的诱导对生存有显著影响。
TGF-β分泌、端粒酶阳性肿瘤中的端粒酶活性以及产生端粒酶特异性免疫反应的能力可能作为肾细胞癌的预后标志物。新的方法可能聚焦于攻击TGF-β通路以及诱导端粒酶特异性免疫细胞。