Figure 1. Pleiotropic effects of 4-1BB signaling on cells from the innate, adaptive and regulatory immune system. Streptavidin-4-1BBL (SA-4-1BBL) employed as an adjuvant for tumor-associated antigen (TAA) subunit-based anticancer vaccines positively influences the generation of effector anticancer immune responses. The engagement of SA-4-1BBL with 4-1BB on APCs enhances their activation, antigen uptake and cross-presentation to T cells. T cells. Activated T cells in turn upregulate 4-1BB and become responsive to SA-4-1BBL-mediated co-stimulation, resulting in enhanced T-cell survival and effector functions. Similar effector functions also ensue the engagement of 4-1BB on natural killer (NK) and NKT cells. Importantly, the activation of 4-1BB on effector T cells not only prevents their conversion into regulatory T cells (Tregs) in the tumor microenvironment, but also render them resistant to Treg-mediated immunosuppression. These events culminate in the generation of therapeutic innate and adaptive immune responses against malignant cells.