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NKR-P1C receptor-carbohydrate interaction contributes to antitumor immune response via activation of NK and B cells
Hulíková, Katarína ; Fišerová, Anna (advisor) ; Kročová, Zuzana (referee) ; Turánek, Jaroslav (referee)
Lectin - saccharide interactions and the involved receptors are currently intensively studied for their important role in antimicrobial as well as antitumor immunity. The major cell types participating in carbohydrate recognition are NK, NKT, and B cells. The differentiation of B lymphocytes could be induced by activated NK cells via direct intercellular contact and/or IFN-γ release. Our research is focused on NK cell receptors of C-type lectin-like family recognizing carbohydrate epitopes of glycoproteins. Synthetic glycoconjugates with terminal N- acetyl-D-glucosamines on polyamidoamine (GN8P) or calix[4]arene (GN4C) scaffold used in this study, exerted the highest binding affinity to activating isoforms of rodent NKR-P1 (A and C) receptor. The aim of the presented dissertation thesis was to elucidate, how Nkr-p1c gene divergence, between C57BL/6 (NK1.1-positive, NKR- P1CB6) and BALB/c (NK1.1-negative, NKR-P1CBALB/c) mouse strains, could affect NK cell activation and subsequent triggering of B lymphocyte effector functions using GN8P and GN4C as NKR-P1C prototype ligands. We demonstrated, that GN8P increased mRNA expression for NKR-P1C receptor, IFN-γ synthesis and lytic activity of NK cells, antigen-specific (anti-KLH, anti-DNP, and anti-B16F10) IgG (particularly IgG2a) formation, number of...
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NKR-P1C receptor-carbohydrate interaction contributes to antitumor immune response via activation of NK and B cells
Hulíková, Katarína ; Fišerová, Anna (advisor) ; Kročová, Zuzana (referee) ; Turánek, Jaroslav (referee)
Lectin - saccharide interactions and the involved receptors are currently intensively studied for their important role in antimicrobial as well as antitumor immunity. The major cell types participating in carbohydrate recognition are NK, NKT, and B cells. The differentiation of B lymphocytes could be induced by activated NK cells via direct intercellular contact and/or IFN-γ release. Our research is focused on NK cell receptors of C-type lectin-like family recognizing carbohydrate epitopes of glycoproteins. Synthetic glycoconjugates with terminal N- acetyl-D-glucosamines on polyamidoamine (GN8P) or calix[4]arene (GN4C) scaffold used in this study, exerted the highest binding affinity to activating isoforms of rodent NKR-P1 (A and C) receptor. The aim of the presented dissertation thesis was to elucidate, how Nkr-p1c gene divergence, between C57BL/6 (NK1.1-positive, NKR- P1CB6) and BALB/c (NK1.1-negative, NKR-P1CBALB/c) mouse strains, could affect NK cell activation and subsequent triggering of B lymphocyte effector functions using GN8P and GN4C as NKR-P1C prototype ligands. We demonstrated, that GN8P increased mRNA expression for NKR-P1C receptor, IFN-γ synthesis and lytic activity of NK cells, antigen-specific (anti-KLH, anti-DNP, and anti-B16F10) IgG (particularly IgG2a) formation, number of...
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Multivalentní glykomika v imunoterapii experimentálních nádorů
Vannucci, Luca ; Pospíšil, Miloslav ; Krist, Pavel ; Křen, Vladimír ; Huliková, Katarína ; Luptovcová, Martina ; Svoboda, Jan ; Kuldová, Markéta ; Bezouška, Karel ; Rossmann, Pavel ; Difato, Francesco ; Mosca, F. ; Fišerová, Anna
Lectin-like receptors can modulate the cytotoxic, regulatory and dendritic cell responses by their interactions. GN8 multivalent glycoconjugates are able to internalize inside and activate NKR-P1 positive cells inducing production of IFN-gamma and expression of CD69. The final effect is a modulation of anticancer immunity with reduction of cancer growth
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Interakce glycodendrimérů s nádorovým mikroprostředím
Pospíšil, Miloslav ; Vannucci, Luca ; Luptovcová, Martina ; Svoboda, Jan ; Huliková, Katarína ; Kuldová, Miloslava ; Bezouška, Karel ; Krist, Pavel ; Pešta, M. ; Fišerová, Anna
Potentiation of immunological parameters by multivalent glycodendrimers (PAMAM-GlcNAc8) against experimental mouse melanoma and rat colon or glioma cancer. PAMAM –GlcNAc8 induce biological effects at different levels of cancer microenvironmental components and concern both, effector and cancer cells
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Imunomodulační glykodendrimery mají afinitu k endoteliím nádorových a embryonálních cév. Mikroskopické průkazy a perspektivy využití
Vannucci, Luca ; Fišerová, Anna ; Krist, Pavel ; Křen, Vladimír ; Huliková, Katarína ; Luptovcová, Martina ; Rossmann, Pavel ; Difato, F. ; Mosca, F. ; Pospíšil, Miloslav
Glycodendrimers coated with N-acetyl-glucosamine and labeled with a fluorescent dye demonstrate special tropism to neogenerated endothelia in cancer capillaries. Same distribution was observed by confocal microscopy in the new vessels of rat embryo abdominal wall, as in placenta and yolk sack endothelia. Results suggests the presence of a commun target on evoluting endothelia, the nature of which is under investigation.
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Interakce glykodendrimerů s nádorovým mikroprostředím
Pospíšil, Miloslav ; Vannucci, Luca ; Luptovcová, Martina ; Svoboda, Jan ; Huliková, Katarína ; Kuldová, Markéta ; Fišerová, Anna
During carcinogenesis and cancer development tissues undergo to important modifications with creation of a specific cancer microenvironment. Locally, the immune system is challenged by tumor-secreted active biological molecules (eg. cytokines, growth factors, NO, lactic acid) that can impair the activation of an effective anticancer response. The use of glycodendrimers targeting immune cells of innate immunity can rescue the activation and stimulate the immune responses, operating through lectin-like receptors.
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