Induction of maturation and activation of human dendritic cells: A mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer

Four day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 μg/ml for 48 hrs. The expression of surface molecules was analyzed by flow cytometry. The ability of Qu Spez-educated DC to stimulate T cells was analyzed by allogeneic mixed lymphocyte reaction and activation of Melan-A/MART-1-specific M77-80 CD8+T cells. Cytokines in cell free culture supernatant was analyzed by cytokine bead array assay.VA Qu Spez stimulated DCs presented with increased expression of antigen presenting molecule HLA-DR and of co-stimulatory molecules CD40, CD80 and CD86. The VA Qu Spez also induced the secretion of inflammatory cytokines IL-6 and IL-8. Further, Qu Spez-educated DC stimulated CD4+T cells in a allogeneic mixed lymphocyte reaction and activated melanoma antigen Melan-A/MART-1-specific M77-80 CD8+T cells as evidenced by increased secretion of TNF-α and IFNγ.The VA preparations stimulate the maturation and activation of human DCs, which may facilitate anti-tumoral immune responses. These results should assist in understanding the immunostimulatory properties of VA preparations and improving the therapeutic strategies.VA preparations are aqueous extracts from Viscum album (also known as European mistletoe) consisting of different types of lectins [1-3]. In addition to mistletoe lectins (ML), biologically active components of VA preparations include viscotoxins, several enzymes, peptides (such as viscumamide), amino acids, thiols, amines, polysaccharides, cyclitoles, lipids, phytosterols, triterpines, flavonoids, phenylpropanes and minerals [3,4]. VA preparations have been used as a complimentary therapy in cancer. Several studies have reported the clinical benefits of VA preparations in cancer patients [5,6]. Treatment with VA preparations or purified ML has also been shown to be associated with tumor regression in several experimental models [7,8]. The mechanisms underlying the anti-tumoral activity of VA preparations are complex and not completely