Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK cell function occurring in MM.

• MeSH
• biologické markery MeSH
• buňky NK imunologie   metabolismus   MeSH
• cílená molekulární terapie MeSH
• cytotoxicita imunologická MeSH
• imunita MeSH
• imunomodulace účinky léků   MeSH
• lidé MeSH
• management nemoci MeSH
• mnohočetný myelom diagnóza   etiologie   metabolismus   terapie   MeSH
• náchylnost k nemoci MeSH
• nádorové mikroprostředí účinky léků   imunologie   MeSH
• prognóza MeSH
• receptory buněk NK genetika   metabolismus   MeSH
• T-lymfocyty - podskupiny imunologie   metabolismus   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes.

• MeSH
• frekvence genu genetika   MeSH
• fúze genů MeSH
• fylogeneze MeSH
• genom genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• koně genetika   MeSH
• lektinové receptory NK-buněk - podrodina A genetika   MeSH
• molekulární sekvence - údaje MeSH
• počítačová simulace MeSH
• receptory buněk NK chemie   genetika   metabolismus   MeSH
• savčí chromozomy genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie aminokyselin MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This work reveals new structural relationships in the complex process of the interaction between activation receptors of natural killer cells (rat NKR-P1, human CD69) and novel bivalent carbohydrate glycomimetics. The length, glycosylation pattern and linker structure of receptor ligands were examined with respect to their ability to precipitate the receptor protein from solution, which simulates the in vivo process of receptor aggregation during NK cell activation. It was found that di-LacdiNAc triazole compounds show optimal performance, reaching up to 100% precipitation of the present protein receptors, and achieving high immunostimulatory activities without any tendency to trigger activation-induced apoptosis. In the synthesis of the compounds tested, two enzymatic approaches were applied. Whereas a β-N-acetylhexosaminidase could only glycosylate one of the two acceptor sites available with yields below 10%, the Y284L mutant of human placental β1,4-galactosyltransferase-1 worked as a perfect synthetic tool, accomplishing even quantitative glycosylation at both acceptor sites and with absolute regioselectivity for the C-4 position. This work insinuates new directions for further ligand structure optimisation and demonstrates the strong synthetic potential of the mutant human placental β1,4-galactosyltransferase-1 in the synthesis of multivalent glycomimetics and glycomaterials.

• MeSH
• aktivace lymfocytů účinky léků   imunologie   MeSH
• beta-N-acetylhexosaminidasy metabolismus   MeSH
• biomimetika metody   MeSH
• buňky NK chemie   účinky léků   imunologie   metabolismus   MeSH
• CD antigeny imunologie   metabolismus   MeSH
• diferenciační antigeny T-lymfocytů imunologie   metabolismus   MeSH
• galaktosyltransferasy genetika   metabolismus   MeSH
• imunoprecipitace MeSH
• krysa rodu rattus MeSH
• lektiny typu C agonisté   imunologie   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• molekulární mimikry MeSH
• mutace MeSH
• placenta enzymologie   MeSH
• polysacharidy chemická syntéza   farmakologie   MeSH
• receptory buněk NK agonisté   imunologie   metabolismus   MeSH
• rekombinantní proteiny genetika   metabolismus   MeSH
• těhotenství MeSH
• vazba proteinů účinky léků   imunologie   MeSH
• vazebná místa účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH