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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| Format: | Article |
| Language: | Russian |
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St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2018-06-01
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| Series: | Медицинская иммунология |
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| Online Access: | https://www.mimmun.ru/mimmun/article/view/1541 |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-55d82abeb5a845fca8999827edb477a9 |
| institution | Kabale University |
| issn | 1563-0625 2313-741X |
| language | Russian |
| publishDate | 2018-06-01 |
| publisher | St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists |
| record_format | Article |
| series | Медицинская иммунология |
| spelling | doaj-art-55d82abeb5a845fca8999827edb477a92025-08-20T03:37:44ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2018-06-0120335336410.15789/1563-0625-2018-3-353-3641018ROLE OF TNFα/TNF-R1-SIGNALING PATHWAY IN CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST GLIOBLASTOMA CELL LINEST. V. Tyrinova0S. V. Mishinov1O. Yu. Leplina2A. A. Alshevskaya3Yu. D. Kurochkina4E. A. Oleynik5А. V. Kalinovskiy6Yu. A. Lopatnikova7S. V. Chernov8V. V. Stupak9S. V. Sennikov10A. A. Ostanin11E. R. Chernykh12Institute of Fundamental and Clinical ImmunologyNovosibirsk Research Ya.L. Tsivyan Institute of Traumatology and OrthopedicsInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyFederal Neurosurgical CenterInstitute of Fundamental and Clinical ImmunologyFederal Neurosurgical CenterNovosibirsk Research Ya.L. Tsivyan Institute of Traumatology and OrthopedicsInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyDendritic 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.https://www.mimmun.ru/mimmun/article/view/1541dendritic cellsinterferon-alphatumor necrosis factor alphatnf-r1glioblastoma multiforme |
| spellingShingle | 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 Медицинская иммунология dendritic cells interferon-alpha tumor necrosis factor alpha tnf-r1 glioblastoma multiforme |
| title | 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_short | 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 |
| topic | dendritic cells interferon-alpha tumor necrosis factor alpha tnf-r1 glioblastoma multiforme |
| url | https://www.mimmun.ru/mimmun/article/view/1541 |
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