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IL-15 and type I interferon are required for activation of tumoricidal NK cells by virus-infected dendritic cells.
- Source :
-
Cancer research [Cancer Res] 2011 Apr 01; Vol. 71 (7), pp. 2497-506. Date of Electronic Publication: 2011 Feb 09. - Publication Year :
- 2011
-
Abstract
- There is increasing evidence that natural killer (NK) cells play an important role in antitumor immunity following dendritic cell (DC) vaccination. Little is known, however, about the optimal stimulation of DCs that favors NK activation in tumor-bearing hosts. In this study, we demonstrate that treatment with toll-like receptor (TLR) ligands and infection with a mutant vesicular stomatitis virus (VSV-ΔM51) both induced DC maturation. Further, inoculation of these DCs led to robust NK-mediated protection against tumor challenge. Strikingly, only VSV-ΔM51-infected DCs were capable of suppressing the growth of established tumors, suggesting that additional signals provided by viral infection may be required to activate tumoricidal NK cells in tumor-bearing hosts. VSV-ΔM51 infection of DCs induced greater type I interferon (IFN I) production than TLR ligand treatment, and disruption of the IFN I pathway in DCs eliminated their ability to induce NK activation and tumor protection. However, further studies indicated that IFN I alone was not sufficient to activate NK cells, especially in the presence of a tumor, and DC-derived IL-15 was additionally required for tumoricidal NK activation. These results suggest that induction of IFN I by VSV-ΔM51 allows DCs to overcome tumor-associated immunosuppression and facilitate IL-15-mediated priming of tumoricidal NK cells. Thus, the mode of DC maturation should be carefully considered when designing DC-based cancer immunotherapies.
- Subjects :
- Animals
Cancer Vaccines immunology
Female
Interferon Regulatory Factor-3 immunology
Interferon Regulatory Factor-3 metabolism
Interferon Type I
Ligands
Melanoma, Experimental immunology
Mice
Mice, Inbred C57BL
Signal Transduction
Toll-Like Receptors immunology
Toll-Like Receptors metabolism
Dendritic Cells immunology
Dendritic Cells virology
Immunotherapy, Adoptive methods
Interleukin-15 immunology
Killer Cells, Natural immunology
Melanoma, Experimental therapy
Vesiculovirus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 71
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 21307131
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-10-3025