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Interferon- α -inducible Dendritic Cells Matured with OK-432 Exhibit TRAIL and Fas Ligand Pathway-mediated Killer Activity

View Article: PubMed Central - PubMed

ABSTRACT

Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing activity in response to some pathogens and cytokines. These antigen-presenting and tumour killing abilities may provide a breakthrough in cancer immunotherapy. However, the mechanisms underlying this killer DC activity have not been fully proven, despite the establishment of interferon-α (IFN-α)-generated killer DCs (IFN-DCs). Here mature IFN-DCs (mIFN-DCs), generated from IFN-DCs primed with OK-432 (streptococcal preparation), exhibited elevated expression of CD86 and human leukocyte antigen-DR (minimum criteria for DC vaccine clinical trials) as well as antigen-presenting abilities comparable with those of mature IL-4-DCs (mIL-4-DCs). Interestingly, the killing activity of mIFN-DCs, which correlated with the expression of CD56 (natural killer cell marker) and was activated via the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand pathway, was stronger than that of IFN-DCs and remarkably stronger than that of mIL-4-DCs. Therefore, mIFN-DCs exhibit great potential as an anti-cancer vaccine that would promote both acquired immunity and direct tumour killing.

No MeSH data available.


The killing activity of mIFN-DCs is stronger than that of IFN-DCs and, particularly, mIL-4-DCs.(a) CFSE-labelled K562 cells were incubated with indicated DCs at a ratio of 50:1 for 18 h. Incubated cells were subsequently subjected to flow cytometry and gated on a FSC and SSC dot plot to identify single cells. Subsequently, the gated cells were subgated according to CFSE and PI staining. DC killing activities are shown as percentages in the dot plot panels (representative of N = 11). (b) DC killing activity against K562 cells is indicated in the box plot (N = 11). *p < 0.05, **p < 0.01.
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f5: The killing activity of mIFN-DCs is stronger than that of IFN-DCs and, particularly, mIL-4-DCs.(a) CFSE-labelled K562 cells were incubated with indicated DCs at a ratio of 50:1 for 18 h. Incubated cells were subsequently subjected to flow cytometry and gated on a FSC and SSC dot plot to identify single cells. Subsequently, the gated cells were subgated according to CFSE and PI staining. DC killing activities are shown as percentages in the dot plot panels (representative of N = 11). (b) DC killing activity against K562 cells is indicated in the box plot (N = 11). *p < 0.05, **p < 0.01.

Mentions: The killing activity of DCs against K562 cells was investigated using flow cytometry. In a representative experiment, IFN-DCs exhibited a killing activity of 17.1%, compared with 40.3% by mIFN-DCs (Fig. 5a), indicating a significant increase only in mIFN-DCs relative to IFN-DCs (Fig. 5b). Moreover, mIFN-DCs showed remarkably enhanced killing activity against K562 cells when compared with mIL-4-DCs. Unexpectedly, we did not observe a significant increase in tumour killing activity by mIL-4-DCs following priming with OK-432 (Fig. 5b). Accordingly, we next focused on the mechanisms underlying this enhanced tumour killing by mIFN-DCs.


Interferon- α -inducible Dendritic Cells Matured with OK-432 Exhibit TRAIL and Fas Ligand Pathway-mediated Killer Activity
The killing activity of mIFN-DCs is stronger than that of IFN-DCs and, particularly, mIL-4-DCs.(a) CFSE-labelled K562 cells were incubated with indicated DCs at a ratio of 50:1 for 18 h. Incubated cells were subsequently subjected to flow cytometry and gated on a FSC and SSC dot plot to identify single cells. Subsequently, the gated cells were subgated according to CFSE and PI staining. DC killing activities are shown as percentages in the dot plot panels (representative of N = 11). (b) DC killing activity against K562 cells is indicated in the box plot (N = 11). *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5304184&req=5

f5: The killing activity of mIFN-DCs is stronger than that of IFN-DCs and, particularly, mIL-4-DCs.(a) CFSE-labelled K562 cells were incubated with indicated DCs at a ratio of 50:1 for 18 h. Incubated cells were subsequently subjected to flow cytometry and gated on a FSC and SSC dot plot to identify single cells. Subsequently, the gated cells were subgated according to CFSE and PI staining. DC killing activities are shown as percentages in the dot plot panels (representative of N = 11). (b) DC killing activity against K562 cells is indicated in the box plot (N = 11). *p < 0.05, **p < 0.01.
Mentions: The killing activity of DCs against K562 cells was investigated using flow cytometry. In a representative experiment, IFN-DCs exhibited a killing activity of 17.1%, compared with 40.3% by mIFN-DCs (Fig. 5a), indicating a significant increase only in mIFN-DCs relative to IFN-DCs (Fig. 5b). Moreover, mIFN-DCs showed remarkably enhanced killing activity against K562 cells when compared with mIL-4-DCs. Unexpectedly, we did not observe a significant increase in tumour killing activity by mIL-4-DCs following priming with OK-432 (Fig. 5b). Accordingly, we next focused on the mechanisms underlying this enhanced tumour killing by mIFN-DCs.

View Article: PubMed Central - PubMed

ABSTRACT

Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing activity in response to some pathogens and cytokines. These antigen-presenting and tumour killing abilities may provide a breakthrough in cancer immunotherapy. However, the mechanisms underlying this killer DC activity have not been fully proven, despite the establishment of interferon-&alpha; (IFN-&alpha;)-generated killer DCs (IFN-DCs). Here mature IFN-DCs (mIFN-DCs), generated from IFN-DCs primed with OK-432 (streptococcal preparation), exhibited elevated expression of CD86 and human leukocyte antigen-DR (minimum criteria for DC vaccine clinical trials) as well as antigen-presenting abilities comparable with those of mature IL-4-DCs (mIL-4-DCs). Interestingly, the killing activity of mIFN-DCs, which correlated with the expression of CD56 (natural killer cell marker) and was activated via the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand pathway, was stronger than that of IFN-DCs and remarkably stronger than that of mIL-4-DCs. Therefore, mIFN-DCs exhibit great potential as an anti-cancer vaccine that would promote both acquired immunity and direct tumour killing.

No MeSH data available.