Mechanisms of action of BCG: towards a new individualized therapeutic approach?
Saint, F.; Patard, J.J.; Salomon, L.; Alamé, W.; Cicco, A.; Abbou, C.C.; Chopin, D.
Progres en Urologie Journal de l'Association Francaise d'Urologie et de la Societe Francaise d'Urologie 10(6): 1118-1126
2000
ISSN/ISBN: 1166-7087 PMID: 11217546 Document Number: 512309
A better knowledge of antitumour immunity and the mechanisms allowing the tumour to overcome the host's immune surveillance has led to progress in the understanding of the mechanisms of action of Bacille Calmette-Guérin (BCG), as the local intravesical immune response is intimately related to the interaction of three systems: the host (the patient), the BCG (mycobacteria) and the tumour. This interaction gives rise to a cascade of immunological events, some of which are essential to the protective action of BCG against relapse and tumour progression. The immune response to BCG is currently considered to comprise three phases. First of all, the BCG adheres to the urothelium and is then phagocytosed by antigen-presenting cells. This phase corresponds to early release of so-called inflammatory cytokines (IL1, IL6, IL8). These cytokines could be responsible for certain adverse effects, but could also participate in cytotoxic phenomena. The second phase consists of recognition of bacterial antigens by helper CD4 lymphocytes, which mainly release IL2 and IFNg (Th1 response). This cellular activation leads to the third phase: amplification of cytotoxic populations capable of killing tumour cells: CD8, gd lymphocytes, macrophages, NK, LAK, BAK cells. All these cells also produce cytokines, which participate in 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 allow the elaboration of more effective immunization protocols by defining an individualized therapeutic approach.