NK Dendritic Cells Expanded in IL-15 Exhibit Antitumor Responses In Vivo

Chaudhry, Umer I.; Plitas, George; Burt, Bryan M.; Kingham, T. Peter; Raab, Jesse R.; DeMatteo, Ronald P.

doi:10.4049/jimmunol.179.7.4654

Cited by 23 publications

(14 citation statements)

References 33 publications

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“…In this regard, NKDC expanded in IL-15 had to be pretreated with IL-12 plus IL-18 to exhibit antitumor activity. 39 In any case, rodent data showing lesser toxicity and a much more consistent immunostimulatory profile back the choice of IL-15 over IL-2 for immunotherapy. 40 Indeed, the hydrodynamic hIL-15 gene transfer has clear biologic effects in our hands, and we believe that it could be used in combination with other immunotherapy agents to enhance their effectiveness, as has already been documented with the recombinant protein.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

et al. 2008

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“…There have been several reports of NKDCs in mice that exhibit both NK-like and DC-like characteristics. The murine NKDCs seem to be heterogeneous, and some subsets were shown to be generated in the presence of IL-18 and CpG (25)(26)(27). In humans, however, the concept of NKDCs has not been generally accepted because researchers have failed to induce and find human counterparts of murine NKDCs (29)(30)(31).…”

Section: Cd11cmentioning

confidence: 99%

“…In murine, a distinct subset of DCs exhibits a phenotype of NK cells and is called NKDCs (24)(25)(26)(27). The other subset of murine DCs exerts lytic activity and produces IFN-g (28).…”

mentioning

confidence: 99%

Involvement of CD56brightCD11c+ Cells in IL-18–Mediated Expansion of Human γδ T Cells

Tsuda

Yamanishi

et al. 2011

The Journal of Immunology

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γδ T cells are considered to be innate lymphocytes that play an important role in host defense against tumors and infections. We recently reported that IL-18 markedly amplified γδ T cell responses to zoledronate (ZOL)/IL-2. In an extension of this finding, we analyzed the mechanism underlying the IL-18–mediated expansion of γδ T cells. After incubation of PBMCs with ZOL/IL-2/IL-18, the majority of the cells expressed γδ TCR, and the rest mostly exhibited CD56brightCD11c+ under the conditions used in this study. CD56brightCD11c+ cells were derived from a culture of CD56intCD11c+ cells and CD14+ cells in the presence of IL-2 and IL-18 without the addition of ZOL. They expressed IL-18Rs, HLA-DR, CD25, CD80, CD83, CD86, and CD11a/CD18. In addition, they produced IFN-γ, TNF-α, but not IL-12, when treated with IL-2/IL-18, and they exerted cytotoxicity against K562 cells, thus exhibiting characteristics of both NK cells and dendritic cells. Incubation of purified γδ T cells with CD56brightCD11c+ cells in the presence of ZOL/IL-2/IL-18 resulted in the formation of massive cell clusters and led to the marked expansion of γδ T cells. However, both conventional CD56−/intCD11chigh dendritic cells induced by GM-CSF/IL-4 and CD56+CD11c− NK cells failed to support the expansion of γδ T cells. These results strongly suggest that CD56brightCD11c+ cells play a key role in the IL-18–mediated proliferation of γδ T cells.

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“…IKDC might be considered as a subpopulation of the so-called "NKDC" (containing all CD11c ϩ NK1.1 ϩ cells) (20,21). However, it is noteworthy that the B220 Ϫ fraction of NKDC was not significantly different from bona fide NK cells for all the hallmark criteria that the manuscript will describe (our unpublished data).…”

Section: Phenotypic Definition and Isolation Of Ikdcmentioning

confidence: 99%

Trans-Presentation of IL-15 Dictates IFN-Producing Killer Dendritic Cells Effector Functions

Ullrich

Bonmort

Mignot

et al. 2008

The Journal of Immunology

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IFN-producing killer dendritic cells (IKDC) were initially described as B220+CD11c+CD3−NK1.1+ tumor-infiltrating cells that mediated part of the antitumor effects of the combination therapy with imatinib mesylate and IL-2. In this study, we show their functional dependency on IL-15 during homeostasis and inflammatory processes. Trans-presentation of IL-15 by IL-15Rα allows dramatic expansion of IKDC in vitro and in vivo, licenses IKDC for TRAIL-dependent killing and endows IKDC with immunizing potential, all three biological attributes not shared by B220−NK cells. However, IL-15 down-regulates the capacity of IKDC to induce MHC class I- or II-restricted T cell activation in vitro. Trans-presentation of IL-15 by IL-15Rα allows IKDC to respond to TLR3 and TLR4 ligands for the production of CCL2, a chemokine that is critical for IKDC trafficking into tumor beds (as described recently). We conclude that IKDC represent a unique subset of innate effectors functionally distinguishable from conventional NK cells in their ability to promptly respond to IL-15-driven inflammatory processes.

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NK Dendritic Cells Expanded in IL-15 Exhibit Antitumor Responses In Vivo

Cited by 23 publications

References 33 publications

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

Involvement of CD56brightCD11c+ Cells in IL-18–Mediated Expansion of Human γδ T Cells

Trans-Presentation of IL-15 Dictates IFN-Producing Killer Dendritic Cells Effector Functions

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