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Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia

2001; Elsevier BV; Volume: 29; Issue: 6 Linguagem: Inglês

10.1016/s0301-472x(01)00636-1

1873-2399

Miwako Narita, Masuhiro Takahashi, Aichun Liu, Kohji Nikkuni, Tatsuo Furukawa, Ken Toba, Satoru Koyama, Kazue Takai, Masayoshi Sanada, Yoshifusa Aizawa,

T-cell and B-cell Immunology

ObjectiveTo 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.Materials and MethodsLeukemia cells of 30 patients with AML were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α. 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.ResultsIn 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.ConclusionsEscape 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.