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  • Title: Superantigen-activated mononuclear cells induce apoptosis in transitional cell carcinoma.
    Author: Perabo FG, Willert PL, Wirger A, Schmidt DH, Von Ruecker A, Mueller SC.
    Journal: Anticancer Res; 2005; 25(5):3565-73. PubMed ID: 16101181.
    Abstract:
    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. MATERIALS AND 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. CONCLUSION: 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.
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