While the primary mechanism is thought to be direct de-repression of CD8+ T cell activity by blocking CTLA-4 antagonism of the T cell costimulatory molecule CD28, recent studies have demonstrated that CTLA-4 blockade has multiple anti-tumor effects, including the reversal of T regulatory cell (Treg) mediated immunosuppression in the tumor microenvironment (81). The gene discussed is CD28; the disease is neoplasm.