Analysis of the immunologic mechanism of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors: distribution and function of immune cells.

Abstract

Intravesical bacillus Calmette-Guerin (BCG) administration has been used as an adjuvant therapy after transurethral resection for superficial bladder cancer, but the exact mechanisms of its antitumor activity are not yet known. The aim of this study was to characterize the immunologic aspects of antitumor activity of BCG using an animal model. C3H/He inbred mice and murine bladder tumor cell line, MBT-2 were used. The changes in immune cells such as helper T cells, suppressor T cells, macrophages and natural killer cells in the bladder and spleen were analysed by immunohistochemical method in intravesical BCG instilled in normal bladder, MBT-2 implanted after electrocauterization of the bladder mucosa and MBT-2 implanted and intravesical BCG treated group. The changes in natural killer cell activity of the splenocytes and peritoneal lymphocytes were evaluated using 51chromium release assay at regular time intervals following intraperitoneal BCG instillation. The prophylactic anticancer effect was evaluated by observing the tumor growth in the intravesically BCG treated group after intravesical MBT-2 implantation. In immunohistochemical examination, a remarkable infiltration of macrophage and helper T cell was observed in the lamina propria of the bladder, and the helper and suppressor T cells ratio (Th/Ts ratio) was increased after intravesical BCG therapy. In 51chromium release assay, enhanced natural killer cell activity of the splenocytes and peritoneal lymphocytes was observed after intraperitoneal BCG inoculation. The growth of implanted tumor was suppressed following intravesical instillation of BCG. These results suggest that the antitumor activity of BCG is not related to the simple inflammatory reaction but to the local and systemic immune response in which helper T lymphocytes and mononuclear cells play an important role.