Mechanisms of action of BCG: towards an individualized therapeutic approach?

A better knowledge of antitumour immunity and the mechanisms allowing the t umour to overcome the host's immune surveillance has led to progress in the understanding of the mechanisms of action of Bacille Calmette-Guerin (BCG) , as the local intravesical immune response is intimately related to the in teraction of three systems: the host (the patient), the BCG (mycobacteria) and the tumour. This interaction gives rise to a cascade of immunological e vents, some of which are essential to the protective action of BCG against relapse and tumour progression. The immune response to BCG is currently con sidered to comprise three phases. First of all, the BCG adheres to the urot helium and is then phagocytosed by antigen-presenting cells. This phase cor responds to early release of so-called inflammatory cytokines (IL1, IL6, IL 8). These cytokines could be responsible for certain adverse effects, but c ould also participate in cytotoxic phenomena. The second phase consists of recognition of bacterial antigens by helper CD 4 lymphocytes, which mainly release IL2 and IFNg (Th1 response). This cellu lar activation lead to the third phase: amplification of cytotoxic populati ons capable of killing tumour cells: CD8, gd lymphocytes, macrophages, NK, LAK, BAK cells. All these cells also produce cytokines, which participate i n regulation of the immune response. The understanding of these mechanisms of action, urinary cytokine assays, a better definition of cytotoxic cells and their role, molecular analysis of the tumour and probably certain genetic characteristics of the host will a llow the elaboration of more effective immunization protocols by defining a n individualized therapeutic approach.