Characterization of monocyte-derived dendritic cells maturated with IFN-alpha.
Dendritic cells (DC) are promising candidates for cancer immunotherapy. These cells can be generated from peripheral blood monocytes cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). In order to obtain full functional capacity, maturation is required, but the most potent reagents such as LPS or polyriboinosinic polyribocytidylic acid (Poly I:C) are not approved for clinical use. We tested the ability of type I interferon (IFN) to induce such maturation. We found that 24-h IFN-alpha co-culture of day 7 monocyte-derived DC generated with GM-CSF and IL-4 induces increased numbers of DC positive for CD54 and CD40 together with the co-stimulatory molecule CD80 but not the activation marker CD83. Also, IFN-alpha maturation leads to an increase in IP-10 and MCP-1 chemokine secretion, but only a minor increase in IL-12p40 secretion. In line with this, maturation with IFN-alpha has only a small effect on induction of autologous T-cell stimulatory capacity of the DC. However, an increase in DC allogeneic T-cell stimulatory capacity was observed. These data suggest that IFN-alpha has a potential as a maturation agent used in DC-based cancer vaccine trials, but not as a single reagent.
Svane
I M
IM
Department of Oncology, Herlev University Hospital, Denmark.
Nikolajsen
K
K
Walter
M R
MR
Buus
S
S
Gad
M
M
Claesson
M H
MH
Pedersen
A E
AE
D017209:Apoptosis; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors
D016207:Cytokines; D016898:Interferon-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor