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 cel ls and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myeloge nous leukemia (AML). Using these leukemia-derived dendritic cells, we inves tigated leukemia cell-associated T-cell anergy. Materials and 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 ant igen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocyte s, which were cocultured with leukemia blasts in the first MLC, were cultur ed with leukemia-derived dendritic cells in the second MLC. Results. In cultures of leukemia cells from 21 of 30 patients examined, cel ls 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 abi lity 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 leu kemia cells of M5. The leukemic origin of dendritic cells was suggested by in situ hybridization. By coculture with CD80- leukemia blasts, the respons e of normal lymphocytes to leukemia-derived dendritic cells cultured from t he same individual as that of leukemia blasts was markedly reduced, compare d with the lymphocytes cultured with leukemia blasts from a different indiv idual as leukemia blasts. Conclusions. Escape of leukemia cells from anti-leukemia immunity may be as sociated with T-cell anergy caused by leukemia blasts. The results of the p resent study suggest that leukemia-derived dendritic cells can be applied e fficiently in anti-leukemia immunotherapy. (C) 2001 International Society f or Experimenta. Hematology. Published by Elsevier Science Inc.