Influence of Immunomodulation on Chemically Induced Bladder Tumors

Abstract

The immunosurveillance theory describes that one of the factors responsible for the development of cancer is the extent of the immunoresponse (Klein 1975). Modulation of the immune system is possible by suppression or stimulation. Cyclosporine A is a powerful immunosuppressive drug which is used for the prevention of allograft rejection in organ transplant patients (Morris 1981). It is relatively specific for T lymphocytes and is thought to act by inhibiting the expression of antigen-induced signals from T cells necessary for the subsequent recruitment, proliferation, and maturation of the T-cell-dependent immune response (Lafferty and Borel 1983). In contrast, keyhole-limpet hemocyanin (KLH) is known to produce a nonspecific immune stimulation. Klippel et al. (1977) injected this agent submucosally into the bladder wall of sensitized and nonsensitized rats. A marked inflammatory reaction was noted with a typical mononuclear cell infiltration without ulceration. A measurable antitumor effect in transplantable murine bladder tumors (MBT2) by KLH was reported by Lamm et al. (1982). In contrast, Walsh et al. (1983) could not find any effect of KLH in a chemically induced (FANFT) murine bladder tumor model. We used a well-established model of bladder carcinoma, chemically initiated by N-butyl-N(4hydroxybutyl) nitrosamin (BBN). The following project was performed to evaluate the influence of two contrary immunoregimens on chemically induced bladder cancer.