4-1BB co-stimulatory receptor (4-1BB)

4-1BB, also known as CD137 or TNFRSF9, is a type I transmembrane receptor of the tumor necrosis factor receptor superfamily that acts as a potent immunomodulatory molecule principally expressed inducibly on activated T cells (CD8+ > CD4+), NK cells, and other immune subsets[1][3][5]. Upon engagement with its ligand 4-1BBL (TNFSF9), a trimeric transmembrane protein expressed on antigen-presenting cells, 4-1BB delivers a critical co-stimulatory signal that enhances T cell proliferation, survival, cytokine production (especially IFN-γ), and effector function, particularly amplifying cytotoxic CD8 T cell responses[1][3][5]. This receptor is being actively explored as a therapeutic target in cancer immunotherapy due to its capacity to boost anti-tumor immunity through agonist antibodies or CAR T cell engineering[1][5]. The major intracellular signaling events downstream of 4-1BB include activation of the NF-κB, ERK, and p38 MAPK pathways, leading to anti-apoptotic and pro-proliferative outcomes[1]. However, clinical manipulation of 4-1BB must balance efficacy with safety, as excessive activation can lead to immune-mediated adverse effects, including hepatotoxicity[5].

Other names

CD137TNFRSF9ILA (Induced by lymphocyte activation) receptortumor necrosis factor receptor superfamily member 9

Agonism to stimulate T cell co-stimulation, Activation of downstream NF-κB/ERK/p38 MAPK pathways, Enhancement of cytotoxic T cell function, Induction of pro-survival signals