Role of 4-1BB:4-1BB ligand in cancer immunotherapy.
The activation of T cells plays a central role in antitumor immunity. In order to activate naïve T cells, two key signals are required. Signal one is provided through the T-cell receptor (TCR) while signal two is that of costimulation. The CD28:B7 molecules are one of the best-studied costimulatory pathways, thought to be the main mechanism through which primary T-cell stimulation occurs. However, a number of molecules have been identified which serve to amplify and diversify the T-cell response, following initial T-cell activation. These include the more recently described 4-1BB:4-1BB ligand (4-1BBL) molecules. 4-1BB:4-1BBL are a member of the TNFR:TNF ligand family, which are expressed on T cells and antigen-presenting cells (APCs), respectively. Therapies utilizing the 4-1BB:4-1BBL signaling pathway have been shown to have antitumor effects in a number of model systems. In this paper, we focus on the 4-1BB:4-1BBL costimulatory molecules. In particular, we will describe the structure and function of the 4-1BB molecule, its receptor and how 4-1BB:4-1BBL costimulation has and may be used for the immunotherapy of cancer.
Cheuk
Adam T C
AT
Leukaemia Science Laboratories, Department of Haematological Medicine, Guy's, King's & St Thomas' School of Medicine, King's College London, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, UK.
Mufti
Ghulam J
GJ
Guinn
Barbara-ann
BA
D053330:4-1BB Ligand; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000378:metabolism / Q000627:therapeutic use; D018106:CD28 Antigens / Q000378:metabolism; D019496:Cancer Vaccines / Q000378:metabolism / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D053330:4-1BB Ligand; D015703:Antigens, CD; D018122:B7-1 Antigen; D018106:CD28 Antigens; D019496:Cancer Vaccines; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha