title: Interferon-α-inducible Dendritic Cells Matured with OK-432 Exhibit TRAIL and Fas Ligand Pathway-mediated Killer Activity.
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.
authors.affiliation: Centre for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Nagano, Japan.
authors.forename: Terutsugu
authors.initials: T
authors.lastname: Koya
authors.affiliation: Centre for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Nagano, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Yanagisawa
authors.affiliation: Centre for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Nagano, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.affiliation: Centre for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Nagano, Japan.|Department of Regenerative Medicine, Kanazawa Medical University, Uchinada-Cho, Kahoku-Gun, Ishikawa, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Shimodaira
mesh_terms: D017951:Antigen Presentation; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015232:Dinoprostone / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010844:Picibanil / Q000494:pharmacology*; D061251:Primary Cell Culture; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000276:immunology
chemical_list: D051940:B7-2 Antigen; D019002:CD56 Antigen; C497964:CD86 protein, human; D019496:Cancer Vaccines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006684:HLA-DR Antigens; C508598:IL4 protein, human; D016898:Interferon-alpha; C522918:NCAM1 protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D015847:Interleukin-4; D010844:Picibanil; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone