| Leukemia is a lethal disease to children. Standard treatments for leukemia ,such as chemotherapy and radiation, often achieve a clinical remission ,but it is frequent recurrence and second-line chemotherapies have a poor response rate. The leukemic cell minimal residue and host immunocompromise are mainly the causes of relapse. Because leukemie cells share the ontogeny with professional antigen presenting cells (APC), enhancing the capacity of leukemic cells to present endogenously expressed tumor-associated antigen directly to T cells has recently been intensive focus. Evidences suggest specific cytokines or other agents can enhance APC func-t ion. To clarify the feasibility of DC-based immunotherapy in leukemia, we therefore investigated the biological characteristic of human acute promyelocytic cell line HL-60 responding to protein kinase C activator-phorbol ester(PMA), granulocyte- macrophage colony stimulating factor(GM-C SF), tumor necrosis factor- alpha (TNF- a ) and intcrleukin-4QL-4}.The inyeloid leukemia-derived dendritic-like cells were induced by these factors. Phenotypic DC characteristics of HL-60 dendritic-like cell (HL-6ODC) include morphologic feature, surface antigens CD1a+/CD86+/CD8O+ and RelB expression as well. The anti-tumor effect of cytotoxic T lymphocyte (CTL) induced by HL-6ODC was tested in vitro and in HL-60/SCID mouse xenograft model. Main results and conclusions were as follows. 1. HL-60 shows a homogeneous population of different size, round, suspension growing cells. About one week after culturing with GM-6 CSF , TNF-6Q and IL-4, some fractions appeared to be morphological manifestations of dendritic cell. The surface antigens CD1a and co stimulatory molecule CD86 expressed on the 13th day. On the 15th or 16th day, CD1a and CD86 expression on the co-cultured HL-60 were up to about 14% and 34% respectively, but not CD8O expression. Combined PMA and GM-CSF plus TNF-6Q , the development of HL-60 DC was more pronounced than those without PMA treated. CD1a reached about 20 percent. CD86 and CD8O was about 72% and 19% correspondingly on culture day 7-61. 2.HL-60 proliferation was suppressed and apoptosis was triggered by PMA and TNF-6a. 3.The specific tumor-lyses capability in vitro of CTL activated by HL-6ODC induced by PMA and GM-CSF plus TNF-6a increased significantly. The effective ratio of effectors to target cells is above 10:1.And the vacuolation in nucleus or indentation of cell membrane was found in the injured HL-60 cells. 4.The level of [Ca2+]i decreased significantly in differentiated HL-60 treated with GM-CSF plus TNF-6a then PMA for 3 days. PMA and the tested cytokines alone show no obvious effect on [Ca2+]i in short time. 5. Re1B mRNA was not detectable in HL-60 and could be induced by the stimulations including cytokines as well as PMA and GM-6 CSF plus TNF-6a. Combined PMA with GM-CSF plus TNF, the expression of Re1B mRNA increased and then declined. 6. Constitutive expression of p65, a subunit of Rel/NF-6-6B, was found in HL-60 cells which was up-regulated by PMA within 24h or GM-CSF plus TNF then PMA within 72h , plateaued through about one...
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