Induction of maturation and activation of human dendritic cells: a mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer.
BACKGROUND
Viscum album (VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression.


METHODS
Four day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 microg/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.


RESULTS
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-alpha and IFNgamma.


CONCLUSIONS
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.
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris6, UMR S 872, Paris, 75006, France. sri-ramulu.elluru@crc.jussieu.fr
Sri Ramulu
SR
Elluru
Jean-Paul
JP
Duong van Huyen
Sandrine
S
Delignat
Michel D
MD
Kazatchkine
Alain
A
Friboulet
Srini V
SV
Kaveri
Jagadeesh
J
Bayry
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000494:pharmacology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000494:pharmacology; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D028182:Viscum album / Q000737:chemistry*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha