Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session

357 - Glioblastoma multiforme cells are sensitive to lysis mediated by killer dendritic cells via granule-dependent and death receptor-dependent mechanisms of cytotoxicity


14 Dec 2018


Poster Display session


Tamara Tyrinova


Annals of Oncology (2018) 29 (suppl_10): x11-x16. 10.1093/annonc/mdy485


T. Tyrinova1, O. Leplina1, S. Mishinov2, M. Tikhonova1, A. Kalinovskiy3, S. Chernov3, V. Stupak2, A. Ostanin1, E. Chernykh1

Author affiliations

  • 1 Laboratory Of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 630099 - Novosibirsk/RU
  • 2 Neurosurgery Department, Novosibirsk Research Institute of Traumatology and Orthopedics them. Y.L.Tsivyana, 630091 - Novosibirsk/RU
  • 3 Neurosurgery Department, Federal Neurosurgical Center, 630087 - Novosibirsk/RU


Abstract 357


Glioblastoma multiforme (GB) is the most common type of primary brain tumors, that virtually always relapses, despite initial treatment with surgical resection, radio- and chemotherapy. Nowadays new promising approaches are developed in treating GB based on dendritic cell (DC) vaccines for the enhancement of the anti-tumor immune response. IFNα-induced monocyte-derived DCs possess properties of myeloid DCs, plasmacytoid DCs and NK cells. The present study focuses on the role of death-inducing mechanisms in DC cytotoxicity against GB cells.


The study was conducted in 26 donors and 21 GB patients. DCs were generated by culturing of plastic-adherent peripheral blood mononuclear cells in the presence of GM-CSF and IFN-α followed by the addition of LPS. The tumor cell lines were obtained from tissues of 14 GB patients. DC cytotoxicity against tumor cells was studied using MTT-assay.


Donor DCs induced death of GB cell lines (min-max cytotoxicity 11-80%). The lysis of GB cells was accompanied with the increase of Annexin V+ apoptotic tumor cells. GB cells expressed death receptors TNF-R1, TRAIL-R2 and Fas. To examine death receptor-mediated killer activity, donor DC were pretreated with soluble forms of TNF family receptors. The blocking of TNF-R1-signaling pathway decreased DC cytotoxicity against GB cells by 25% on average. rhTRAIL-R2 or rhFas pretreatment slightly abolished DC cytotoxicity (with an average of 10%). The most blocking effect on DC cytotoxicity against GB cells was observed if DCs were pretreated with concanamicin A, an inhibitor of granule-dependent killing (Δ up to 60%). GB patient DCs were characterized by reduced cytotoxicity against autologous GB cell lines compared to donor values. Low cytotoxicity of patient DCs was associated with decreased level of membrane TNFα (mTNFα), but intact FasL, TRAIL, perforin and granzyme B molecule expression. The addition of IL-2 into patient DCs enhanced cytotoxicity of DCs towards autologous GB cells and increased mTNFα expression on DCs.


Thus, DCs with tumoricidal activity and ex vivo regulation of DC cytotoxic function may become a new approach to obtain effective anti-tumor DC-vaccines.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Elena Chernykh.


Grant of the Foundation of the President of the Russian Federation.


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.