title: Immunobiology and conflicting roles of the human NKG2D lymphocyte receptor and its ligands in cancer.
abstract: Cancers adopt diverse strategies to safeguard their survival, which often involve blinding or incapacitating the immune response, thereby gaining battleground advantage against the host. In immune responses against cancer, an important stimulatory lymphocyte receptor is NKG2D because the tumor-associated expression of its ligands promotes destruction of malignant cells. However, with advanced human cancers profound changes unfold wherein NKG2D and its ligands are targeted or exploited for immune evasion and suppression. This negative imprinting on the immune system may be accompanied by another functional state wherein cancer cells coopt expression of NKG2D to complement the presence of its ligands for self-stimulation of tumor growth and presumably malignant progression. This review emphasizes these conflicting functional dynamics at the immunity-cancer biology interface in humans, within an overview of the immunobiology of NKG2D and mechanisms underlying the regulation of its ligands in cancer, with reference to instructive clinical observations and translational approaches.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Gazzar
authors.forename: Veronika
authors.initials: V
authors.lastname: Groh
authors.forename: Thomas
authors.initials: T
authors.lastname: Spies
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001327:Autoimmune Diseases / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D018450:Disease Progression; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007157:Immunologic Surveillance / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D035683:MicroRNAs / Q000276:immunology; D058990:Molecular Targeted Therapy; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology
chemical_list: D016207:Cytokines; C120528:HCST protein, human; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008024:Ligands; D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic
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