4-1BB (CD137, tumor necrosis factor receptor superfamily 9) is an inducible costimulatory receptor expressedon activated T andnatural killer (NK)cells. 4-1BB ligationon T cells triggers a signaling cascade that results in upregulation of anti-apoptotic molecules, cytokine secretion, andenhanced effector function.In dys functional T cells that have a decreased cytotoxic capacity, 4-1BB ligation demon strates a potentability torestore effector functions. On NK cells, 4-1BB signaling can increase antibody-dependentcell-mediated cytotoxicity. Agonistic monoclonal antibodies targeting 4-1BB have been developed to harness 4-1BB signaling for cancer immunotherapy.