Superantigen-activated mononuclear cells induce apoptosis in transitional cell carcinoma.
BACKGROUND
Superantigens are among the most potent T-cell mitogens known. Since T-cell activation and T-cell-derived cytokines play a role in the immune response associated with intravesical Bacillus Calmette-Guerin (BCG) application, this study was initiated to explore the fundamental aspects of a potential new immunomodulatory therapy for superficial bladder cancer. Since Superantigen-induced cytotoxicity is mediated by apoptosis, the effects of SEB (staphylococcal enterotoxin B)-Superantigen-activated PBMC (peripheral blood mononuclear cells) on bladder cancer cells were evaluated with regard to Fas/Fas-ligand-based interactions.


METHODS
Whether SEB can induce Fas-ligand expression on PBMC and the extent of cytokine secretion were examined by flow cytometry and specific ELISA. In addition, whether the SEB-activated PBMC are able to induce apoptosis in transitional cell carcinoma cells (TCC) was evaluated in co-culture experiments.


RESULTS
It was shown that SEB induced pronounced time- but not dose-dependent specific Fas-ligand expression on PBMC, lasting 1 h to 7 h after initiation of the experiment. Cleaved soluble Fas-ligand was detected in the culture supernatants 24 h after stimulation, but not earlier. Further, a strong time-dependent secretion of cytokines IL-2, IFN-gamma and TNF-alpha released from the SEB-stimulated PBMC was shown. In co-culture experiments, it was demonstrated that SEB-activated PBMC significantly induced apoptosis in TCC cells. The released cytokines from SEB-treated PBMC demonstrated only a minor, not significant, apoptotic response in TCC cells.


CONCLUSIONS
This first evaluation of the possible mode of action of a Superantigen opens the door for extended studies of this interesting approach to the treatment of bladder cancer.
Perabo
Frank G E
FG
Department of Urology, University of Bonn, 53105 Bonn, Germany. perabo@lycos.com
Willert
Patricia L
PL
Wirger
Andreas
A
Schmidt
Doris H
DH
Von Ruecker
Alexander
A
Mueller
Stefan C
SC
D017209:Apoptosis / Q000276:immunology*; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D018089:Superantigens / Q000276:immunology* / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology
D016207:Cytokines; D004768:Enterotoxins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D018089:Superantigens; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal