Characterization of Primary Renal Carcinoma Cultures

Abstract

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.

The Notch and TGF-β Signaling Pathways Contribute to the Aggressiveness of Clear Cell Renal Cell Carcinoma

“…Interestingly, elevated levels of TGF-β1 in serum from CCRCC patients are correlated with unfavorable outcome of the disease [26], [28], [29]. Hence, the tumor microenvironment in CCRCC is rich in TGF-β1.…”

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…Indeed, gene expression studies in large cohorts of RCC-bearing patients have suggested that some molecules such as IL-1, IL-6, TNF-α, C1q, and C1r could be implicated in the initiation and promotion of an intratumor inflammatory cascade (Peri, Devarajan, Yang, Knudson, & Balachandran, 2013;Romero et al, 2006;Tan et al, 2011). The RCC tumor cells probably orchestrate this inflammatory environment as suggested by the presence of several cytokines in the supernatant of RCC primary cultures, including IL-8, IL-10, TGF-β, GM-CSF, TNF-α, and VEGF (Gogusev, Augusti, Chrétien, & Droz, 1993;Knoefel et al, 1997;Lahn et al, 1999;Lee, Chun, Nadiminty, Lou, & Gao, 2007;Sievers et al, 2007). Interestingly, some of them can be found in the serum of RCC-bearing patients Wald et al, 2014), supporting their active production throughout RCC development.…”

Interleukin-6 as an emerging regulator of renal cell cancer

“…IL-6 is secreted by many renal cancer cell lines and is abundant in the serum of 50% of the patients with metastatic [39,40] renal cell cancer [39][40][41][42]. Moreover, it has been demonstrated that primary RCC cultures secrete elevated levels of IL-6 [43]. Investigated RCC cell lines expressed IL-6 mRNA, produced IL-6, and expressed the soluble and membrane-bound gp130 chain of the IL-6 receptor.…”