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.
Original language | English |
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Article number | 2898 |
Number of pages | 19 |
Journal | International Journal of Molecular Sciences |
Volume | 21 |
Issue number | 8 |
DOIs | |
Publication status | Published - 21 Apr 2020 |
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