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The local immune response to mycobacteria is complex, but mycobacterial antigen presentation by phagocytes to T helper cells is the pivotal interaction. Bacille Calmette-Guérin (BCG) vaccination is associated with the development of antituberculosis immunity but not necessarily with antitumor immunity. Animal studies have shown that an intact host immune system is required for the antitumor activity of BCG. Immunosuppressed and, particularly, T cell-depleted individuals fail to respond to BCG immunotherapy. Clinical and laboratory evidence suggest that the antitumor activity is concentrated at the site of BCG administration, which reinforces the view that local immune mechanisms are responsible for this phenomenon.