Purpose: 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. Materials and Methods: 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. Results: We were able to establishprimary 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-β, VEGF and IL-8. High TGF-β 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. Conclusion: TGF-β 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-β pathway and on induction of telomerase-specific immune cells.