Characterization of primary renal carcinoma cultures.
OBJECTIVE
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.


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 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.


CONCLUSIONS
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.
Sievers
Elisabeth
E
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Dreimuller
Patrick
P
Haferkamp
Axel
A
Schmidt-Wolf
Ingo G H
IG
Buchler
Markus W
MW
Schmidt
Jan
J
Marten
Angela
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019098:Telomerase / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019098:Telomerase