Biochemical and immunological characteristics of 4-1BB (CD137) receptor and ligand and potential applications in cancer therapy.
4-1BB (CD 137) is a member of the tumor necrosis factor receptor (TNFR) superfamily that is expressed primarily on activated T cells. Crosslinking of the 4-1BB receptor activates an intracellular signal cascade that leads to the activation of NF-kappaB and costimulation of T cell growth. Recent evidence indicates that 4-1BB may preferentially costimulate CD8+ T cell growth and induce cytolytic activity. The cytolytic activity induced by 4-1BB crosslinking is able to eradicate large, well-established, poorly immunogenic tumors and augments allogenic T cell responses in vivo. The 4-1BB/4-1BB ligand costimulatory pathway can provide an alternative T cell costimulatory pathway in the absence of CD28, but may physiologically function as a synergistic or complementary pathway to the CD28 costimulatory pathway. Only some of the basic immunological functions of 4-1BB/4-IBB ligand have been elucidated and much study is required to determine its exact role in T cell activation.
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Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
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D000818:Animals; D015703:Antigens, CD; D018106:CD28 Antigens / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D016853:Muromonab-CD3 / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D009369:Neoplasms / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D018106:CD28 Antigens; D008024:Ligands; D016853:Muromonab-CD3; D016328:NF-kappa B; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9