ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES

Dendritic cells (DCs) of patients with high-grade brain glioma exhibit impaired expression of membrane TNFα associated with low DC cytotoxicity against TNF-R1-expressing tumor cell line HEp-2. To assess the significance of these findings, we investigated a role of TNFα/TNF-R1-signaling pathway in DC...

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Autores principales:	T. V. Tyrinova, S. V. Mishinov, O. Yu. Leplina, A. A. Alshevskaya, Yu. D. Kurochkina, E. A. Oleynik, А. V. Kalinovskiy, Yu. A. Lopatnikova, S. V. Chernov, V. V. Stupak, S. V. Sennikov, A. A. Ostanin, E. R. Chernykh
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2018
Materias:	dendritic cells interferon-alpha tumor necrosis factor alpha tnf-r1 glioblastoma multiforme Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/55d82abeb5a845fca8999827edb477a9
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spelling	oai:doaj.org-article:55d82abeb5a845fca8999827edb477a92021-11-18T08:03:47ZROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES1563-06252313-741X10.15789/1563-0625-2018-3-353-364https://doaj.org/article/55d82abeb5a845fca8999827edb477a92018-06-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1541https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XDendritic cells (DCs) of patients with high-grade brain glioma exhibit impaired expression of membrane TNFα associated with low DC cytotoxicity against TNF-R1-expressing tumor cell line HEp-2. To assess the significance of these findings, we investigated a role of TNFα/TNF-R1-signaling pathway in DC cytotoxic activity against allogenic and autologous cell lines obtained from high-grade glioma tissues. DCs were generated by culturing of plastic-adherent peripheral blood mononuclear cells in presence of GM-CSF and IFNα for 4 d followed by LPS addition for 24 h (IFN-DCs). The tumor cell lines were obtained from tissues of 11 patients with glioblastoma multiforme. According our findings glioblastoma cells were sensitive to lysis mediated by donor IFN-DCs. The level of DC cytotoxic effect against cell lines obtained from different glioma patient tissues varied from 20 to 72.2%. DC lysis of 8 out of 11 glioblastoma cell lines exceeded 40%. Glioblastoma cell lines expressed both TNF-R1 and TNF-R2 receptors, but mostly – TNF-R1. However, rTNFα did not show cytotoxic activity towards glioblastoma cell lines. Blocking of TNFα/TNF-R1-signaling pathway by treating of donor IFN-DCs with soluble rhTNFR1 receptor led to partial decrease of DC cytotoxic activity against 5 out of 6 tested glioblastoma cell lines by 11-40% (median of suppression 24%). Glioblastoma patient IFN-DCs which were characterized by an impairment of TNFα/TNF-R1-signaling pathway lysed these glioblastoma cell lines, however median of DC cytotoxicity was 30% lower than that of donor values (31.5 vs 45.1%; р = 0.003). Cytotoxic activity of IFN-DCs of the glioblastoma patient against autologous tumor cells resistance to TNFα/TNF-R1-signaling pathway was comparable with level of cytotoxicity of donor IFN-DCs. Thus, glioblastoma cells are sensitive to cytotoxic activity of DCs mediated via TNFα/TNF-R1-signaling pathway, but the defect of this mechanism in IFN-DCs of glioblastoma patients determines significant decrease of DC cytotoxicity towards glioblastoma cells.T. V. TyrinovaS. V. MishinovO. Yu. LeplinaA. A. AlshevskayaYu. D. KurochkinaE. A. OleynikА. V. KalinovskiyYu. A. LopatnikovaS. V. ChernovV. V. StupakS. V. SennikovA. A. OstaninE. R. ChernykhSPb RAACIarticledendritic cellsinterferon-alphatumor necrosis factor alphatnf-r1glioblastoma multiformeImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 20, Iss 3, Pp 353-364 (2018)
institution	DOAJ
collection	DOAJ
language	RU
topic	dendritic cells interferon-alpha tumor necrosis factor alpha tnf-r1 glioblastoma multiforme Immunologic diseases. Allergy RC581-607
spellingShingle	dendritic cells interferon-alpha tumor necrosis factor alpha tnf-r1 glioblastoma multiforme Immunologic diseases. Allergy RC581-607 T. V. Tyrinova S. V. Mishinov O. Yu. Leplina A. A. Alshevskaya Yu. D. Kurochkina E. A. Oleynik А. V. Kalinovskiy Yu. A. Lopatnikova S. V. Chernov V. V. Stupak S. V. Sennikov A. A. Ostanin E. R. Chernykh ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES
description	Dendritic cells (DCs) of patients with high-grade brain glioma exhibit impaired expression of membrane TNFα associated with low DC cytotoxicity against TNF-R1-expressing tumor cell line HEp-2. To assess the significance of these findings, we investigated a role of TNFα/TNF-R1-signaling pathway in DC cytotoxic activity against allogenic and autologous cell lines obtained from high-grade glioma tissues. DCs were generated by culturing of plastic-adherent peripheral blood mononuclear cells in presence of GM-CSF and IFNα for 4 d followed by LPS addition for 24 h (IFN-DCs). The tumor cell lines were obtained from tissues of 11 patients with glioblastoma multiforme. According our findings glioblastoma cells were sensitive to lysis mediated by donor IFN-DCs. The level of DC cytotoxic effect against cell lines obtained from different glioma patient tissues varied from 20 to 72.2%. DC lysis of 8 out of 11 glioblastoma cell lines exceeded 40%. Glioblastoma cell lines expressed both TNF-R1 and TNF-R2 receptors, but mostly – TNF-R1. However, rTNFα did not show cytotoxic activity towards glioblastoma cell lines. Blocking of TNFα/TNF-R1-signaling pathway by treating of donor IFN-DCs with soluble rhTNFR1 receptor led to partial decrease of DC cytotoxic activity against 5 out of 6 tested glioblastoma cell lines by 11-40% (median of suppression 24%). Glioblastoma patient IFN-DCs which were characterized by an impairment of TNFα/TNF-R1-signaling pathway lysed these glioblastoma cell lines, however median of DC cytotoxicity was 30% lower than that of donor values (31.5 vs 45.1%; р = 0.003). Cytotoxic activity of IFN-DCs of the glioblastoma patient against autologous tumor cells resistance to TNFα/TNF-R1-signaling pathway was comparable with level of cytotoxicity of donor IFN-DCs. Thus, glioblastoma cells are sensitive to cytotoxic activity of DCs mediated via TNFα/TNF-R1-signaling pathway, but the defect of this mechanism in IFN-DCs of glioblastoma patients determines significant decrease of DC cytotoxicity towards glioblastoma cells.
format	article
author	T. V. Tyrinova S. V. Mishinov O. Yu. Leplina A. A. Alshevskaya Yu. D. Kurochkina E. A. Oleynik А. V. Kalinovskiy Yu. A. Lopatnikova S. V. Chernov V. V. Stupak S. V. Sennikov A. A. Ostanin E. R. Chernykh
author_facet	T. V. Tyrinova S. V. Mishinov O. Yu. Leplina A. A. Alshevskaya Yu. D. Kurochkina E. A. Oleynik А. V. Kalinovskiy Yu. A. Lopatnikova S. V. Chernov V. V. Stupak S. V. Sennikov A. A. Ostanin E. R. Chernykh
author_sort	T. V. Tyrinova
title	ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES
title_short	ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES
title_full	ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES
title_fullStr	ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES
title_full_unstemmed	ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES
title_sort	role of tnfα/tnf-r1-signaling pathway in cytotoxic activity of dendritic cells against glioblastoma cell lines
publisher	SPb RAACI
publishDate	2018
url	https://doaj.org/article/55d82abeb5a845fca8999827edb477a9
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ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINES

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