Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia.
OBJECTIVE
To elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leukemia cell-associated T-cell anergy.


METHODS
Leukemia cells of 30 patients with AML were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha. Cultured leukemia cells were evaluated for antigen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocytes, which were cocultured with leukemia blasts in the first MLC, were cultured with leukemia-derived dendritic cells in the second MLC.


RESULTS
In cultures of leukemia cells from 21 of 30 patients examined, cells with stellate morphology and cell fractions with CD1a(+) and/or CD83(+) were present. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated antigen-presenting ability in leukemia-derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3, or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. The leukemic origin of dendritic cells was suggested by in situ hybridization. By coculture with CD80(-) leukemia blasts, the response of normal lymphocytes to leukemia-derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from a different individual as leukemia blasts.


CONCLUSIONS
Escape of leukemia cells from anti-leukemia immunity may be associated with T-cell anergy caused by leukemia blasts. The results of the present study suggest that leukemia-derived dendritic cells can be applied efficiently in anti-leukemia immunotherapy.
Narita
M
M
School of Health Sciences, Faculty of Medicine, Niigata University, Niigata, Japan. naritami@clg.niigara-u.ac.jp
Takahashi
M
M
Liu
A
A
Nikkuni
K
K
Furukawa
T
T
Toba
K
K
Koyama
S
S
Takai
K
K
Sanada
M
M
Aizawa
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D018920:Coculture Techniques; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor