Tumoricidal activity of monocyte-derived dendritic cells: Evidence for a caspase-8-dependent, Fas-associated death domain-independent mechanism

被引:52
作者
Vanderheyde, N
Aksoy, E
Amraoui, Z
Vandenabeele, P
Goldman, M
Willems, F
机构
[1] Free Univ Brussels, Expt Immunol Lab, B-1070 Brussels, Belgium
[2] State Univ Ghent VIB, Dept Mol Biol, B-9000 Ghent, Belgium
关键词
D O I
10.4049/jimmunol.167.7.3565
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Monocyte-derived dendritic cells (DC) were found to be cytotoxic for several tumor cell lines including Jurkat cells, which were killed through a calcium-independent pathway. K562 cells were resistant, excluding a NK cell-like activity. DC-mediated apoptosis did not involve classical death receptors because it was not reversed by blocking TNF/TNFR, CD95/CD95 ligand, or TNF-related apoptosis-inducing ligand/TNF-related apoptosis-inducing ligand receptor interactions. Fas-associated death domain-deficient, but not caspase-8 deficient, Jurkat cells were killed by DC. Indeed, caspase-8 cleavage was demonstrated in Jurkat cells cocultured with DC, and the use of specific caspase inhibitors confirmed that apoptosis triggered by DC was caspase-8 dependent. Furthermore, the involvement of Bcl-2 family members in the control of DC-mediated apoptosis was demonstrated by Bid cleavage in Jurkat cells cocultured with DC and resistance of Jurkat cells overexpressing Bcl-2 to DC-mediated cytotoxicity. Overall, these data indicate that monocyte-derived DC exert a caspase-8-dependent, Fas associated death domain-independent tumoricidal activity, a finding that could be relevant to their therapeutic use in cancer.
引用
收藏
页码:3565 / 3569
页数:5
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