Generation and characterization of dendritic-like cells derived from translocation (9;22) acute lymphoblastic leukemia blasts.

摘要

Translocation (t)(9;22) occurs in approximately one third of adult acute lymphoblastic leukemia (ALL) patients and is associated with an unfavorable prognosis. Lack of co-stimulatory signals may cause leukemic cells to evade the host immune system. Dendritic cells (DC) are known as the most powerful antigen-presenting cells and leukemia-derived dendritic-like cells are suggested to be useful for immunotherapy in acute and chronic myeloid leukemias. However, there is no such study in ALL. I defined a cytokine treatment [mixture of interleukin (IL)-1beta, IL-3, IL-7, tumor necrosis factor (TNF)-alpha, stem cell factor and CD40 ligand (L)] to generate dendritic-like cells from ALL blasts. These cells had dendritic-like characteristics and were able to induce allogeneic and autologous T cell responses. ALL-derived dendritic-like cells were composed of at least 3 populations characterized by flow cytometric analyses: CD80-/CD86-, CD80-/CD86+ and CD80+/CD86+ cells, which may represent undifferentiated, immature and mature dendritic-like cells, respectively Differentiation was achieved with the combination of CD40L and TNF-alpha as compared to other maturational factors, e.g., CpG oligodeoxynucleotide (ODN) and lipopolysaccharide. Interestingly, the addition of CpG ODN to CD40L and TNF-alpha enhanced maturation. These studies provide a basis for further studies of DC-based immunotherapy in patients with ALL carrying t(9;22) and lead to further research on the role of leukemia-derived dendritic-like cells.