Abstract Book 2010 - CIMT Annual Meeting
Abstract Book 2010 - CIMT Annual Meeting
Abstract Book 2010 - CIMT Annual Meeting
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081 Lion | Tumor biology & interaction with the immune system<br />
Poly(I:C)-electroporated myeloid leukemic cell lines become<br />
highly susceptible to NK cell-mediated killing and phagocytosis<br />
by immature DC<br />
Eva Lion 1 , Sébastien Anguille 1 , 2 , Evelien Smits 1 , Zwi Berneman 1 , 2 , Viggo Van Tendeloo 1<br />
1 Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium<br />
2 Laboratory of Experimental Hematology, Antwerp University Hospital, Antwerp, Belgium<br />
130<br />
Natural killer (NK) cells and dendritic cells (DC) are<br />
proven to exert important functions in anti-tumor<br />
defence. Targeting both immune cells for immunebased<br />
therapy is currently advised. We recently<br />
showed that electroporation (EP) of acute myeloid<br />
leukemic (AML) cell lines with the synthetic double-stranded<br />
RNA TLR3-ligand poly(I:C) enhances<br />
their capacity to act on DC and NK cells. Aside from<br />
the fact that tumor cells themselves become apoptotic<br />
and start to secrete marked amounts of type<br />
I interferon (IFN), they are able to mature DC and<br />
promote NK cell IFN-γ. In this study, we explored the<br />
effect of poly(I:C)-EP AML cell lines on the killing<br />
capacity of NK cells and the phagocytic potential<br />
of DC. Additionally, we assessed these functionalities<br />
in three-party cocultures to see for functional<br />
cross-talk. We hypothesized that poly(I:C)-induced<br />
apoptosis and the presence of IFN-α would increase<br />
the NK cell cytotoxicity. In turn, this could lead to<br />
an increased tumor cell up-take by DC.<br />
All experiments were performed with fresh autologous<br />
monocyte-derived immature DC and purified<br />
NK cells of healthy donors. The K562 and U-937<br />
leukemic cell lines were used as targets. Flow cytometric<br />
detection of cytotoxicity and phagocytosis<br />
was acquired simultaneously. Cytotoxicity was determined<br />
based on the viability (annexin V- propidium<br />
iodide-) of PKH67-labeled AML cells. Phagocytosis<br />
of PKH67+ tumor cells by violet-labeled DC<br />
was expressed as the % PKH67+violet+ cells of all<br />
violet+ DC, selected for single cells.<br />
Our data demonstrate that poly(I:C)-EP of AML<br />
cell lines results in an increased susceptibility to<br />
NK cell-mediated killing (p=0.0023 for K562 and<br />
p
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