Tumoricidal Activity of Monocyte-Derived Dendritic Cells: Evidence for a Caspase-8-Dependent, Fas-Associated Death Domain-Independent Mechanism

  • Vanderheyde N
  • Aksoy E
  • Amraoui Z
  • et al.
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Abstract

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.

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APA

Vanderheyde, N., Aksoy, E., Amraoui, Z., Vandenabeele, P., Goldman, M., & Willems, F. (2001). Tumoricidal Activity of Monocyte-Derived Dendritic Cells: Evidence for a Caspase-8-Dependent, Fas-Associated Death Domain-Independent Mechanism. The Journal of Immunology, 167(7), 3565–3569. https://doi.org/10.4049/jimmunol.167.7.3565

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