Induction of Th1 response by dendritic cells pulsed with autologous melanoma apoptotic bodies.
BACKGROUND
We hypothesize that dendritic cells (DCs) can process antigens from autologous melanoma apoptotic bodies (MABs) and induce effector T cells in melanoma patients.


METHODS
Peripheral blood mononuclear cells were obtained from three stage IV melanoma patients and adherent cells were cultured in complete medium (CM) containing GM-CSF (800 U/ml) and IL-4 (1000 U/ml) for 7 days. Autologous MABs from melanoma cells following actinomycin D treatment (0.5 microgram/ml) for 24 hours, were added to 72 hour DC culture. Autologous effector T cells were cultured in CM containing 60 IU/ml of IL-2 and were stimulated by MAB-pulsed DCs three times at a weekly interval. Effector T cells were harvested at the end of third cycle of DC stimulation.


RESULTS
Using ELISPOT, IFN-gamma production by effector T cells stimulated by MAB-pulsed DCs was significantly higher than that by T cells without DC stimulation. Microscopy demonstrated phagocytosis of MABs by DCs.


CONCLUSIONS
MAB-pulsed DCs are capable of stimulating Th1-directed autologous effector T cells. Pulsing DCs with autologous MABs may be a novel approach in future DC-based immunotherapeutic trials.
Department of Surgery, University of California/Mount Zion Cancer Center, San Francisco 94115, USA.
J W
JW
Chang
M
M
Peng
J E
JE
Vaquerano
Y M
YM
Zhou
R A
RA
Clinton
W C
WC
Hyun
M A
MA
Giedlin
S P
SP
Leong
D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000473:pathology; D010587:Phagocytosis; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000951:Antigens, Neoplasm; D016753:Interleukin-10; D007371:Interferon-gamma