Collectively, these studies demonstrate that 4-1BB signaling in conventional CD4+ T cells not only affect their activation, expansion, survival and establishment of long-term memory [14], but also renders these cells refractory to immunosuppression by Treg cells [13] as well as blocks their conversion into iTreg cells with significant potential for the development of therapeutic vaccines against cancer and chronic infections. The gene discussed is CD4; the disease is cancer.