Analysis of Antitumor Mechanism of Intravesical BCG Therapy in Tumorigenesis(I): Study About T Cell Dependency

Kim, Sun Jin; Lee, Chongwook

Abstract

A study was carried out to define the role of T cells in tumorigenesis and antitumor activity of BCG treatment for superficial transitional cell carcinoma of urinary bladder using an anima1 mode1. We analysed the change of immunocytes and effect on tumor forming rate of BCG in C3H/He inbred mice with bladder tumors induced by N-butyl-N-(4-hydroxybuty1)-nitrosamine(BBN) and determined the relationship between changes of immunocytes and tumor forming rate. The number and distribution of helper(T4), and suppressor/cytotoxic(T8) T cells were studied immunohistochemically in the spleen and urinary bladder. In BBN administered group, helper T cells were increased. in urinary bladder as gross tumor developed, but it seemed to be not effective in tumor prevention, and there was no significant change observed in suppressor/cytotoxic T cells. Depletion of helper T cells in spleen observed in mice with gross tumors suggested the possibility of systemic response to tumor development In BCG treated group, helper in bladder and spleen were all increased markedly and decreased with time sequence. The change of suppressor T cells were not observed. In BBN administered and BCG treated group, the tumor forming rate was initially reduced by 30-40% comparing to the BBN only group, but the rate was subsequently increased gradually with time sequence. The rate became same between 2 groups by 20 weeks. Local reaction as well as cellular immunity which was mediated by systemic immune system appeared to play an important role in antitumor mechanism of BCG Helper T cell was thought to be the major element involved in antitumor activity. Since our result indicated that effect of BCG was time limited, we have to make an effort to modify current method of BCG treatment accordingly.