However, we and others have found that it actually generates a sub-optimal population of differentiated effector-memory cells that have not only variable effector (tumor cell killing) properties, but that can also be hypo-responsive to re-stimulation by melanoma antigens and susceptible to activation-induced cell death (AICD); these have been associated with a loss of CD28, and to lesser extent CD27, and memory function [8]. The gene discussed is CD28; the disease is melanoma.