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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.


Phenotypic comparison of dendritic cells (DCs) stimulated with OK-432.DCs generated from patients (N = 8) were stained with mAbs for typical DC markers and analysed via flow cytometry. The change in mean fluorescence intensity (MFI) was calculated by subtracting the MFI values of the isotype control from the sample values. *p < 0.05; NS, not significant.
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f2: Phenotypic comparison of dendritic cells (DCs) stimulated with OK-432.DCs generated from patients (N = 8) were stained with mAbs for typical DC markers and analysed via flow cytometry. The change in mean fluorescence intensity (MFI) was calculated by subtracting the MFI values of the isotype control from the sample values. *p < 0.05; NS, not significant.

Mentions: We first examined the phenotypic effects of OK-432 on mIFN-DCs and mIL-4-DCs. After OK-432 stimulation, similar remarkable clusters of cells bearing the morphologic features of mature DCs were observed equally among mIFN-DCs and mIL-4-DCs (Fig. 1). A phenotypic assessment of surface markers revealed the increased expression of costimulatory molecules such as CD80 and CD86 on mIFN-DCs, whereas the levels of these markers on mIL-4-DCs had not significantly changed (Fig. 2). Similarly, increases in the levels of CD14 and human leukocyte antigen (HLA)-DR were more evident on mIFN-DCs than on mIL-4-DCs. In contrast, mIL-4-DCs featured more strongly elevated expression of CD40, CD83 and CD197.


Interferon- α -inducible Dendritic Cells Matured with OK-432 Exhibit TRAIL and Fas Ligand Pathway-mediated Killer Activity
Phenotypic comparison of dendritic cells (DCs) stimulated with OK-432.DCs generated from patients (N = 8) were stained with mAbs for typical DC markers and analysed via flow cytometry. The change in mean fluorescence intensity (MFI) was calculated by subtracting the MFI values of the isotype control from the sample values. *p < 0.05; NS, not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304184&req=5

f2: Phenotypic comparison of dendritic cells (DCs) stimulated with OK-432.DCs generated from patients (N = 8) were stained with mAbs for typical DC markers and analysed via flow cytometry. The change in mean fluorescence intensity (MFI) was calculated by subtracting the MFI values of the isotype control from the sample values. *p < 0.05; NS, not significant.
Mentions: We first examined the phenotypic effects of OK-432 on mIFN-DCs and mIL-4-DCs. After OK-432 stimulation, similar remarkable clusters of cells bearing the morphologic features of mature DCs were observed equally among mIFN-DCs and mIL-4-DCs (Fig. 1). A phenotypic assessment of surface markers revealed the increased expression of costimulatory molecules such as CD80 and CD86 on mIFN-DCs, whereas the levels of these markers on mIL-4-DCs had not significantly changed (Fig. 2). Similarly, increases in the levels of CD14 and human leukocyte antigen (HLA)-DR were more evident on mIFN-DCs than on mIL-4-DCs. In contrast, mIL-4-DCs featured more strongly elevated expression of CD40, CD83 and CD197.

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.