Generation of lymphocytes potentiated against leukemic lymphoblasts by stimulation using leukemic cell lysate-pulsed dendritic cells in patients with acute lymphoblastic leukemia and measurement of in vitro anti-leukemic cytotoxicity

Abstract

Using granulocyte-macrophage colony stimulating factor, interleukin4 and tumor necrosis factor α, we generated dendritic cells (DCs) from mononuclear cells isolated from the peripheral blood (PB) of eight patients with acute lymphoblastic leukemia (ALL), who were in complete remission (CR), and pulsed these DCs with leukemic cell lysates. Specific cytotoxicity assays were performed by incubation of effector cells (lymphocytes generated from cryopreserved mononuclear cells isolated in CR state of ALL) and targets (cryopreserved leukemic cells at diagnosis). Patients showing decreased cytotoxicity had poorer clinical courses. When we measured lymphocyte subsets, we found positive correlations between cytotoxicity levels and the proportions of T lymphocytes and CD8+ T lymphocytes, but negative correlations between cytotoxicity levels and the proportions of NK cells and regulatory T lymphocytes. In conclusion, we show here that leukemia-specific autologous DCs can be generated from the PB of ALL patients in CR, that the incubation of these DCs with leukemic cell lysates can generate lymphocytes potentiated against leukemic cells, and that relationships are evident among all of cytotoxicity, lymphocyte subsets, and patient prognosis.