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Acute myeloid leukemic cell lines loaded with synthetic dsRNA trigger IFN-gamma secretion by human NK cells.
- Source :
-
Leukemia research [Leuk Res] 2009 Apr; Vol. 33 (4), pp. 539-46. Date of Electronic Publication: 2008 Oct 09. - Publication Year :
- 2009
-
Abstract
- Natural killer (NK) cells are key players of innate immunity. Besides their major cytotoxic function, NK cells can also produce inflammatory cytokines such as interferon (IFN)-gamma. In this way, NK cells can shape adaptive immune responses through activation of dendritic cells (DC), thereby promoting the bidirectional cross-talk between NK cells and DC. Including this helper function of NK cells in cancer vaccination might be important for the induction of effective T cell responses. Here, we explored the capacity of purified human NK cells to produce IFN-gamma upon two-signal stimulation using different types of acute myeloid leukemia (AML) cells and type I IFN. Based on our previous findings that AML cells produce IFN-alpha upon electroporation with the synthetic double-stranded (ds)RNA polyriboinosinic polyribocytidylic acid (poly(I:C)), we hypothesized that dsRNA-loaded tumor cells provide both signals to elicit an NK cell-driven IFN-gamma production. Our results show that in vitro, NK cells become strong IFN-gamma-secreting cells upon stimulation with specific AML cells and IFN-alpha, with a variable responsiveness against different AML cell lines. Importantly, loading of AML cells with poly(I:C) is an elegant method to provide NK cells with both signals, a feature that could have important clinical implications because it obviates the side effects of systemic cytokine administration. Moreover, in addition to our previous findings that DC become activated upon phagocytosis of poly(I:C)-electroporated AML cells, these data strongly encourage future research on the potential of dsRNA-transfected AML cells and their effect to favor NK-DC cross-talk for the design of leukemia vaccines.
- Subjects :
- Cell Communication immunology
Cell Line, Tumor
Coculture Techniques
Electroporation
Flow Cytometry
Humans
Interferon Inducers immunology
Killer Cells, Natural metabolism
Leukemia, Myeloid, Acute genetics
Poly I-C immunology
Interferon-gamma metabolism
Killer Cells, Natural immunology
Leukemia, Myeloid, Acute immunology
RNA, Double-Stranded immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5835
- Volume :
- 33
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 18845337
- Full Text :
- https://doi.org/10.1016/j.leukres.2008.08.020