The immunomodulatory effects of anti-4-1BB therapy. (A) Agonistic anti-4-1BB mAb therapy induces T-cell proliferation and cytokine secretion. (B) On NK cells, stimulation of 4-1BB enhances ADCC. (C) Agonistic anti-4-1BB mAbs can also stimulate DCs and macrophages to induce antitumor immune responses, and 4-1BB is expressed in tumor-associated vascular endothelium. (D) Bispecific antibodies targeting both 4-1BB and tumor antigens such as HER2 can lock immune effectors and target cells in close proximity and facilitate tumor cell lysis. Mφ, macrophages, TCR, T-cell receptor.