Fas Ligand and TNF-Related Apoptosis-Inducing Ligand Induction on Infiltrating Lymphocytes in Bladder Carcinoma by Bacillus Calmette-Guérin Treatment

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Abstract
Aim: To determine the molecular mechanisms underlying the efficacy of bacillus Calmette-Guérin (BCG) therapy against superficial carcinoma of the urinary bladder, we evaluated the expression of cytotoxic molecules on tumor-infiltrating lymphocytes before and after therapy. Methods: Immunofluorescence staining allowed the specific detection of Fas, Fas ligand (FasL), and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on tumor cells and the respective leukocyte populations in biopsy samples from 6 patients. Results: Significant increases in the infiltration of FasL- and TRAIL-expressing CD4+ T cells and macrophages and FasL-expressing CD8+ T and NK cells were observed after BCG instillation in bladder carcinoma. Moreover, Fas expression was upregulated on tumor cells after BCG instillation. Conclusion: The data suggested that the enhanced infiltration of FasL- and/or TRAIL-expressing leukocytes (CD4+ T cells, CD8+ T cells, natural killer cells and macrophages) and the induction of Fas expression on tumor cells may play an important role in the therapeutic effect of BCG instillation.