Combined stimulation with interleukin-18 and CpG induces murine natural killer dendritic cells to produce IFN-γ and inhibit tumor growth Journal Article

  

Authors:	Chaudhry, U. I.; Kingham, T. P.; Plitas, G.; Katz, S. C.; Raab, J. R.; DeMatteo, R. P.
Article Title:	Combined stimulation with interleukin-18 and CpG induces murine natural killer dendritic cells to produce IFN-γ and inhibit tumor growth
Abstract:	Natural killer dendritic cells (NKDC) are a novel subtype of dendritic cells with natural killer (NK) cell properties. IFN-γ is a pleiotropic cytokine that plays an important role in the innate immune response to tumors. Based on our previous finding that the combination of Toll-like receptor 9 ligand CpG and interleukin (IL)-4 stimulates NKDC to produce IFN-γ, we hypothesized that NKDC are the major IFN-γ-producing dendritic cell subtype and may play a significant role in the host antitumor response. We found that under several conditions in vitro and in vivo NKDC accounted for the majority of IFN-γ production by murine spleen CD11c + cells. IL-18 alone induced NKDC to secrete IFN-γ, and the combination of EL-18 and CpG resulted in a synergistic increase in IFN-γ production, both in vitro and in vivo. NK cells made 26-fold less IFN-γ under the same conditions in vitro, whereas dendritic cells produced a negligible amount. The mechanism of IFN-γ secretion by NKDC depended on IL-12. NKDC selectively proliferated in vitro and in vivo in response to the combination of IL-18 and CpG. Systemic treatment with II.-18 and CpG reduced the number of B16F10 melanoma lung metastases. The mechanism depended on NK1.1 + cells, as their depletion abrogated the effect. IL-18 and CpG activated NKDC provided greater tumor protection than NK cells in IFN-γ -/- mice. Thus, NKDC are the major dendritic cell subtype to produce IFN-γ, The combined use of IL-18 and CpG is a viable strategy to potentiate the antitumor function of NKDC. ©2006 American Association for Cancer Research.
Keywords:	controlled study; dose response; drug potentiation; nonhuman; cell proliferation; animal cell; mouse; animals; mice; animal tissue; dendritic cell; lung neoplasms; animal experiment; animal model; in vivo study; in vitro study; drug effect; mice, inbred c57bl; drug synergism; cancer inhibition; lung metastasis; lymphocyte activation; dendritic cells; dna; gamma interferon; cpg oligodeoxynucleotide; melanoma b16; melanoma, experimental; natural killer cell; killer cells, natural; cell protection; interleukin 12; spleen cell; interleukin 18; cd11 antigen; interleukin-12; interferon type ii; interleukin-18
Journal Title:	Cancer Research
Volume:	66
Issue:	21
ISSN:	0008-5472
Publisher:	American Association for Cancer Research
Date Published:	2006-11-01
Start Page:	10497
End Page:	10504
Language:	English
DOI:	10.1158/0008-5472.can-06-1908
PUBMED:	17079471
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33751266583&partnerID=40&md5=cb1f52bec6369f3b96a861ef6bc1eddc
Notes:	--- - "Cited By (since 1996): 35" - "Export Date: 4 June 2012" - "CODEN: CNREA" - "Source: Scopus"

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