Mechanisms of action of bacillus Calmette-Guérin in the treatment of superficial bladder cancer.

Local immunotherapy with bacillus Calmette-Guérin (BCG) is an effective treatment to prevent recurrence and progression of superficial bladder cancer, but the antitumor mechanism of action of BCG remains unclear. There are some experimental and clinical data suggesting that BCG antigens are processed not only by immunocompetent cells but also by urothelial cells and tumor cells. The foreign antigen may be presented at the cell surface by major histocompatibility complex (MHC) class II molecules and recognized by CD4 cells. The cytotoxic effect could result from the direct activity of CD4 cells or from the cytotoxic effect of released cytokines and the activation of other cytotoxic cells [cytolytic T-lymphocytes CTLs; CD8 cells), macrophages, natural killer (NK) or lymphokine-activated killer (LAK) cells]. These mechanisms are also involved in tumor rejection, and the identification of some specific tumor rejection antigens presented to specific CTLs could provide new therapeutic approaches.