Anti-tumoral capabilities of effector cells after IFN-alpha or CpG-motif treatment of cocultured dendritic cells.
BACKGROUND
Ex vivo expansion of monocyte-derived dendritic cells (mDCs) and subsequent coculture with autologous cytokine-induced killer (CIK) cells is an established system to create specific and non-specific anti-tumoral immunity. mDCs constitute the most frequently applied DC subset in clinical studies. One recently published approach to optimize the immunological functions of the DC/CIK cell system is the replacement of interleukin (IL)-4 by interferon (IFN)-alpha in the maturation process of the DCs.


METHODS
The expressions of relevant surface antigens of IL-4-DCs and IFNalpha-DCs by flow cytometry and the anti-tumoral activation of effector cells cocultured with both types of DCs using cytotoxicity assays were compared. In addition, short-term coculture experiments with both types of DCs and IFNgamma-LAK effector cells were performed and compared with standard CIK cell coculture experiments.


RESULTS
Regarding the expressions of functionally relevant surface markers, no differences could be detected for CD80, CD83, and HLA-DR between IFNalpha-DCs and IL-4-DCs, whereas the mean fluorescence intensities of CD40, CD86, CD54, and HLA-ABC were decreased and the expression of CD14 was increased for IFNgamma-DCs. Moreover, no enhancement of cytotoxicity of cocultured CIK cells against tumor cell lines (A498 and SW480) was detected by the use of IFNalpha-DCs. Additionally, coculture experiments with IFNgamma-LAK cells were performed and unexpectedly higher lysis rates in comparison with the established IL-4-DC/CIK coculture model was observed. Early incubation of the mDCs with several CpG-ODNs failed to increase the anti-tumoral cytotoxicity of the cocultured IFNgamma-LAK cells.


CONCLUSIONS
These results demonstrate that in the mDC/CIK cell system, IFNalpha-DCs are not superior in inducing anti-tumoral cytotoxicity and even moderately inferior regarding the expression of functionally relevant surface markers compared with IL-4-DCs.
Erhardt
Michael
M
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Schmidt-Wolf
Ingo G H
IG
Sievers
Elisabeth
E
Frank
Susanne
S
Strehl
John
J
von Lilienfeld-Toal
Marie
M
Gorschlüter
Marcus
M
D000954:Antigens, Surface / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D018899:CpG Islands; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D009369:Neoplasms / Q000628:therapy*; D009841:Oligonucleotides / Q000494:pharmacology
D000954:Antigens, Surface; D016898:Interferon-alpha; D009841:Oligonucleotides; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor