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

Terutsugu Koya; Ryu Yanagisawa; Yumiko Higuchi; Kenji Sano; Shigetaka Shimodaira

doi:10.1038/srep42145

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

Sci Rep. 2017 Feb 13:7:42145. doi: 10.1038/srep42145.

Authors

Terutsugu Koya¹, Ryu Yanagisawa¹, Yumiko Higuchi¹, Kenji Sano², Shigetaka Shimodaira^{1

3}

Affiliations

¹ Centre for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Nagano, Japan.
² Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan.
³ Department of Regenerative Medicine, Kanazawa Medical University, Uchinada-Cho, Kahoku-Gun, Ishikawa, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigen Presentation
B7-2 Antigen / genetics
B7-2 Antigen / immunology
CD56 Antigen / genetics
CD56 Antigen / immunology
Cancer Vaccines / biosynthesis
Cell Differentiation / drug effects
Cytotoxicity, Immunologic*
Dendritic Cells / cytology
Dendritic Cells / drug effects*
Dendritic Cells / immunology
Dinoprostone / pharmacology
Fas Ligand Protein / genetics*
Fas Ligand Protein / immunology
Gene Expression Regulation
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
HLA-DR Antigens / genetics
HLA-DR Antigens / immunology
Humans
Immunophenotyping
Interferon-alpha / pharmacology*
Interleukin-4 / pharmacology*
Monocytes / cytology
Monocytes / drug effects
Monocytes / immunology
Picibanil / pharmacology*
Primary Cell Culture
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand / genetics*
TNF-Related Apoptosis-Inducing Ligand / immunology

Substances

B7-2 Antigen
CD56 Antigen
CD86 protein, human
Cancer Vaccines
FASLG protein, human
Fas Ligand Protein
HLA-DR Antigens
IL4 protein, human
Interferon-alpha
NCAM1 protein, human
TNF-Related Apoptosis-Inducing Ligand
TNFSF10 protein, human
Interleukin-4
Picibanil
Granulocyte-Macrophage Colony-Stimulating Factor
Dinoprostone