{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T10:07:47Z","timestamp":1760609267192,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u0420\u043e\u0441\u0441\u0438\u0439\u0441\u043a\u0438\u0439 \u0424\u043e\u043d\u0434 \u0424\u0443\u043d\u0434\u0430\u043c\u0435\u043d\u0442\u0430\u043b\u044c\u043d\u044b\u0445 \u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0439 (\u0420\u0424\u0424\u0418)","award":["16-34-00711, 20-015-00284"],"award-info":[{"award-number":["16-34-00711, 20-015-00284"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 IFN\u03b1-induced DCs (IFN-DCs) of glioblastoma multiforme patients express low levels of membrane TNF\u03b1 molecule (mTNF\u03b1) and have impaired TNF\u03b1\/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 TNF\u03b1\/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 TNF\u03b1\/TNFR1-mediated lysis, which was associated with low TNF\u03b1 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 TNF\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms21082898","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T04:15:13Z","timestamp":1587528913000},"page":"2898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Defective Regulation of Membrane TNF\u03b1 Expression in Dendritic Cells of Glioblastoma Patients Leads to the Impairment of Cytotoxic Activity against Autologous Tumor Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7987-2017","authenticated-orcid":false,"given":"Tamara","family":"Tyrinova","sequence":"first","affiliation":[{"name":"Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"},{"name":"Institute of Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Leplina","sequence":"additional","affiliation":[{"name":"Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Mishinov","sequence":"additional","affiliation":[{"name":"Novosibirsk Research Institute of Traumatology and Orthopedics them. Y.L.Tsivyana, 630091 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Tikhonova","sequence":"additional","affiliation":[{"name":"Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeniya","family":"Dolgova","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630099 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7650-4331","authenticated-orcid":false,"given":"Anastasiya","family":"Proskurina","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630099 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vyacheslav","family":"Stupack","sequence":"additional","affiliation":[{"name":"Novosibirsk Research Institute of Traumatology and Orthopedics them. Y.L.Tsivyana, 630091 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-9382","authenticated-orcid":false,"given":"Sergey","family":"Bogachev","sequence":"additional","affiliation":[{"name":"Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, 630099 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Ostanin","sequence":"additional","affiliation":[{"name":"Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Chernykh","sequence":"additional","affiliation":[{"name":"Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/icb.1997.35","article-title":"The role of dendritic cells in T cell activation","volume":"75","author":"Ni","year":"1997","journal-title":"Immunol. 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