Abstract
One of the most exciting fields in modern medicine is immunotherapy, treatment which looks to harness the power of the immune system to fight disease. A particularly effective strategy uses antibodies designed to influence the activity levels of the immune system. Here we look at two receptors - TIGIT and DNAM-1 - which bind the same ligands but have opposite effects on immune cells, earning them the label `paired receptors'. Importantly, natural killer cells and cytotoxic T cells express both of these receptors, and in certain cases their effector functions are dictated by TIGIT or DNAM-1 signaling. Agonist and antagonist antibodies targeting either TIGIT or DNAM-1 present many therapeutic options for diseases spanning from cancer to auto-immunity. In this review we present cases in which the modulation of these receptors holds potential for the development of novel therapies.
Keywords:
DNAM-1; NK cells; TIGIT; autoimmune disease; cancer; immunotherapy.
MeSH terms
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology*
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Antineoplastic Agents, Immunological / therapeutic use*
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Autoimmune Diseases / drug therapy*
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology
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Autoimmune Diseases / pathology
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Gene Expression Regulation
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Humans
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Immunotherapy / methods*
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology
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Killer Cells, Natural / pathology
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Neoplasms / drug therapy*
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Neoplasms / genetics
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Neoplasms / immunology
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Neoplasms / pathology
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Protein Binding
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Receptor Cross-Talk / immunology
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Receptors, Immunologic / agonists
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology*
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Signal Transduction
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / pathology
Substances
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Antigens, Differentiation, T-Lymphocyte
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Antineoplastic Agents, Immunological
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CD226 antigen
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Receptors, Immunologic
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TIGIT protein, human