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Defective regulation of membrane TNFα expression in dendritic cells of glioblastoma patients leads to the impairment of cytotoxic activity against autologous tumor cells. / Tyrinova, Tamara; Leplina, Olga; Mishinov, Sergey et al.

In: International Journal of Molecular Sciences, Vol. 21, No. 8, 2898, 21.04.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

Tyrinova, T, Leplina, O, Mishinov, S, Tikhonova, M, Dolgova, E, Proskurina, A, Stupack, V, Bogachev, S, Ostanin, A & Chernykh, E 2020, 'Defective regulation of membrane TNFα expression in dendritic cells of glioblastoma patients leads to the impairment of cytotoxic activity against autologous tumor cells', International Journal of Molecular Sciences, vol. 21, no. 8, 2898. https://doi.org/10.3390/ijms21082898

APA

Tyrinova, T., Leplina, O., Mishinov, S., Tikhonova, M., Dolgova, E., Proskurina, A., Stupack, V., Bogachev, S., Ostanin, A., & Chernykh, E. (2020). Defective regulation of membrane TNFα expression in dendritic cells of glioblastoma patients leads to the impairment of cytotoxic activity against autologous tumor cells. International Journal of Molecular Sciences, 21(8), [2898]. https://doi.org/10.3390/ijms21082898

Vancouver

Tyrinova T, Leplina O, Mishinov S, Tikhonova M, Dolgova E, Proskurina A et al. Defective regulation of membrane TNFα expression in dendritic cells of glioblastoma patients leads to the impairment of cytotoxic activity against autologous tumor cells. International Journal of Molecular Sciences. 2020 Apr 21;21(8):2898. doi: 10.3390/ijms21082898

Author

BibTeX

@article{53d9d5c6bf994827a220a8a1151d19ae,
title = "Defective regulation of membrane TNFα expression in dendritic cells of glioblastoma patients leads to the impairment of cytotoxic activity against autologous tumor cells",
abstract = "Besides an antigen-presenting function and ability to induce antitumor immune responses, dendritic cells (DCs) possess a direct tumoricidal activity. We previously reported that monocyte-derived IFNα-induced DCs (IFN-DCs) of glioblastoma multiforme patients express low levels of membrane TNFα molecule (mTNFα) and have impaired TNFα/TNF-R1-mediated cytotoxicity against immortalized tumor cell line HEp-2. However, whether the observed defect could affect killer activity of glioma patient DCs against autologous tumor cells remained unclear. Here, we show that donor IFN-DCs possess cytotoxic activity against glioblastoma cell lines derived from a primary tumor culture. Granule-mediated and TNFα/TNF-R1-dependent pathways were established as the main mechanisms underlying cytotoxic activity of IFN-DCs. Glioblastoma patient IFN-DCs showed lower cytotoxicity against autologous glioblastoma cells sensitive to TNFα/TNFR1-mediated lysis, which was associated with low TNFα mRNA expression and high TACE/ADAM-17 enzyme activity. Recombinant IL-2 (rIL-2) and human double-stranded DNA (dsDNA) increased 1.5-fold cytotoxic activity of patient IFN-DCs against autologous glioblastoma cells. dsDNA, but not rIL-2, enhanced the expression of TNFα mRNA and decreased expression and activity of TACE/ADAM-17 enzyme. In addition, dsDNA and rIL-2 stimulated the expression of perforin and granzyme B (in the presence of dsDNA), suggesting the possibility of enhancing DC cytotoxicity against autologous glioblastoma cells via various mechanisms.",
keywords = "Dendritic cells, Glioblastoma, Granule-dependent cytotoxicity, TACE/ADAM-17, TNFα, GLIOMA-CELLS, PATHWAYS, INTERLEUKIN-2, FAS LIGAND, APOPTOSIS, TNF alpha, ACTIVATED PROTEIN-KINASE, TRAIL, granule-dependent cytotoxicity, INTERFERON-ALPHA, IN-VITRO, dendritic cells, glioblastoma, ANTIGEN",
author = "Tamara Tyrinova and Olga Leplina and Sergey Mishinov and Marina Tikhonova and Evgeniya Dolgova and Anastasiya Proskurina and Vyacheslav Stupack and Sergey Bogachev and Alexander Ostanin and Elena Chernykh",
year = "2020",
month = apr,
day = "21",
doi = "10.3390/ijms21082898",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

RIS

TY - JOUR

T1 - Defective regulation of membrane TNFα expression in dendritic cells of glioblastoma patients leads to the impairment of cytotoxic activity against autologous tumor cells

AU - Tyrinova, Tamara

AU - Leplina, Olga

AU - Mishinov, Sergey

AU - Tikhonova, Marina

AU - Dolgova, Evgeniya

AU - Proskurina, Anastasiya

AU - Stupack, Vyacheslav

AU - Bogachev, Sergey

AU - Ostanin, Alexander

AU - Chernykh, Elena

PY - 2020/4/21

Y1 - 2020/4/21

N2 - Besides an antigen-presenting function and ability to induce antitumor immune responses, dendritic cells (DCs) possess a direct tumoricidal activity. We previously reported that monocyte-derived IFNα-induced DCs (IFN-DCs) of glioblastoma multiforme patients express low levels of membrane TNFα molecule (mTNFα) and have impaired TNFα/TNF-R1-mediated cytotoxicity against immortalized tumor cell line HEp-2. However, whether the observed defect could affect killer activity of glioma patient DCs against autologous tumor cells remained unclear. Here, we show that donor IFN-DCs possess cytotoxic activity against glioblastoma cell lines derived from a primary tumor culture. Granule-mediated and TNFα/TNF-R1-dependent pathways were established as the main mechanisms underlying cytotoxic activity of IFN-DCs. Glioblastoma patient IFN-DCs showed lower cytotoxicity against autologous glioblastoma cells sensitive to TNFα/TNFR1-mediated lysis, which was associated with low TNFα mRNA expression and high TACE/ADAM-17 enzyme activity. Recombinant IL-2 (rIL-2) and human double-stranded DNA (dsDNA) increased 1.5-fold cytotoxic activity of patient IFN-DCs against autologous glioblastoma cells. dsDNA, but not rIL-2, enhanced the expression of TNFα mRNA and decreased expression and activity of TACE/ADAM-17 enzyme. In addition, dsDNA and rIL-2 stimulated the expression of perforin and granzyme B (in the presence of dsDNA), suggesting the possibility of enhancing DC cytotoxicity against autologous glioblastoma cells via various mechanisms.

AB - Besides an antigen-presenting function and ability to induce antitumor immune responses, dendritic cells (DCs) possess a direct tumoricidal activity. We previously reported that monocyte-derived IFNα-induced DCs (IFN-DCs) of glioblastoma multiforme patients express low levels of membrane TNFα molecule (mTNFα) and have impaired TNFα/TNF-R1-mediated cytotoxicity against immortalized tumor cell line HEp-2. However, whether the observed defect could affect killer activity of glioma patient DCs against autologous tumor cells remained unclear. Here, we show that donor IFN-DCs possess cytotoxic activity against glioblastoma cell lines derived from a primary tumor culture. Granule-mediated and TNFα/TNF-R1-dependent pathways were established as the main mechanisms underlying cytotoxic activity of IFN-DCs. Glioblastoma patient IFN-DCs showed lower cytotoxicity against autologous glioblastoma cells sensitive to TNFα/TNFR1-mediated lysis, which was associated with low TNFα mRNA expression and high TACE/ADAM-17 enzyme activity. Recombinant IL-2 (rIL-2) and human double-stranded DNA (dsDNA) increased 1.5-fold cytotoxic activity of patient IFN-DCs against autologous glioblastoma cells. dsDNA, but not rIL-2, enhanced the expression of TNFα mRNA and decreased expression and activity of TACE/ADAM-17 enzyme. In addition, dsDNA and rIL-2 stimulated the expression of perforin and granzyme B (in the presence of dsDNA), suggesting the possibility of enhancing DC cytotoxicity against autologous glioblastoma cells via various mechanisms.

KW - Dendritic cells

KW - Glioblastoma

KW - Granule-dependent cytotoxicity

KW - TACE/ADAM-17

KW - TNFα

KW - GLIOMA-CELLS

KW - PATHWAYS

KW - INTERLEUKIN-2

KW - FAS LIGAND

KW - APOPTOSIS

KW - TNF alpha

KW - ACTIVATED PROTEIN-KINASE

KW - TRAIL

KW - granule-dependent cytotoxicity

KW - INTERFERON-ALPHA

KW - IN-VITRO

KW - dendritic cells

KW - glioblastoma

KW - ANTIGEN

UR - http://www.scopus.com/inward/record.url?scp=85083966495&partnerID=8YFLogxK

U2 - 10.3390/ijms21082898

DO - 10.3390/ijms21082898

M3 - Article

C2 - 32326230

AN - SCOPUS:85083966495

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 8

M1 - 2898

ER -

ID: 24190768