Title
Poly(I:C) enhances the susceptibility of leukemic cells to NK cell cytotoxicity and phagocytosis by DCPoly(I:C) enhances the susceptibility of leukemic cells to NK cell cytotoxicity and phagocytosis by DC
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Vaccine & Infectious Disease Institute (VAXINFECTIO)
Publication type
article
Publication
Subject
Human medicine
Source (journal)
PLoS ONE
Volume/pages
6(2011):6, p. e20952,1-e20952,10
ISSN
1932-6203
Article Reference
e20952
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
α Active specific immunotherapy aims at stimulating the host's immune system to recognize and eradicate malignant cells. The concomitant activation of dendritic cells (DC) and natural killer (NK) cells is an attractive modality for immune-based therapies. Inducing immunogenic cell death to facilitate tumor cell recognition and phagocytosis by neighbouring immune cells is of utmost importance for guiding the outcome of the immune response. We previously reported that acute myeloid leukemic (AML) cells in response to electroporation with the synthetic dsRNA analogue poly(I:C) exert improved immunogenicity, demonstrated by enhanced DC-activating and NK cell interferon-γ-inducing capacities. To further invigorate the potential of these immunogenic tumor cells, we explored their effect on the phagocytic and cytotoxic capacity of DC and NK cells, respectively. Using single-cell analysis, we assessed these functionalities in two- and three-party cocultures. Following poly(I:C) electroporation AML cells become highly susceptible to NK cell-mediated killing and phagocytosis by DC. Moreover, the enhanced killing and the improved uptake are strongly correlated. Interestingly, tumor cell killing, but not phagocytosis, is further enhanced in three-party cocultures provided that these tumor cells were upfront electroporated with poly(I:C). Altogether, poly(I:C)-electroporated AML cells potently activate DC and NK cell functions and stimulate NK-DC cross-talk in terms of tumor cell killing. These data strongly support the use of poly(I:C) as a cancer vaccine component, providing a way to overcome immune evasion by leukemic cells.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/eabe6f/619a1ed3.pdf
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