Costimulation can change the balance between regulatory and effector T-cell responses to lymphoma. A schematic is shown to illustrate this balance; it does not attempt to incorporate important features such as the role of antigen-presenting cells. (A) At presentation, although some effector T cells infiltrate the tumor, they are not activated and the immune response is dominated by T_reg cells and thus tolerance. (B) After administration of a costimulatory stimulus, here an agnostic monoclonal antibody directed against CD137, the conventional (effector) T cells become activated and exert cytotoxic effects on the lymphoma. Depletion of T_reg cells accentuates the cytotoxicity. Professional illustration by Marie Dauenheimer.