Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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4-1BB Ligand
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Amino Acid Sequence
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Animals
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Antigens, CD
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B7-1 Antigen / metabolism
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B7-1 Antigen / therapeutic use
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CD28 Antigens / metabolism
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Cancer Vaccines / metabolism
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Cancer Vaccines / therapeutic use
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Clinical Trials as Topic
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Disease Models, Animal
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Humans
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Mice
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Molecular Sequence Data
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Neoplasms / immunology
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Neoplasms / therapy*
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism*
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Receptors, Nerve Growth Factor / physiology
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism*
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Receptors, Tumor Necrosis Factor / physiology
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Signal Transduction / immunology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism*
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Tumor Necrosis Factor-alpha / physiology
Substances
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4-1BB Ligand
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Antigens, CD
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B7-1 Antigen
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CD28 Antigens
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Cancer Vaccines
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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TNFRSF9 protein, human
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TNFSF9 protein, human
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Tnfrsf9 protein, mouse
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Tnfsf9 protein, mouse
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Tumor Necrosis Factor-alpha