In vitro induction of a dendritic cell phenotype in primary human acute myelogenous leukemia (AML) blasts alters the chemokine release profile and increases the levels of T cell chemotactic CCL17 and CCL22.

摘要

Immunotherapy is now considered in acute myelogenous leukemia (AML). A dendritic cell (DC) phenotype can be induced in primary human AML cells by in vitro culture in the presence of various cytokine combinations. The aim was to investigate whether this phenotypic alteration is associated with altered chemokine release. AML cells were cultured according to four protocols that have been characterized in detail for AML-DC induction: (1) granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) days 1-14 and tumor necrosis factor-alpha (TNF-alpha) for days 6-14, (2) GM-CSF + IL-4 + TNF-alpha + FMS-like tyrosine kinase 3-ligand (Fl3-L) for 8 days, (3) GM-CSF + IL-4 + TNF-alpha + Flt3-L + stem cell factor (SCF) + transforming growth factor-beta1 (TGF-beta1) for 8 days, and (4) 25 Gy gamma-irradiation combined with culture in the presence of GM-CSF + SCF + IL-3 for 4 days. Significantly increased AML-DC release of CCL17 and CCL22 was observed for protocols 1, 2, and 3, whereas effects on CCL2-5, CXCL8, and CXCL10 differed in all protocols. Neutralization studies using a transwell migration assay demonstrated the increased level of CCL17 and CCL22 release was important for AML-DC chemotaxis of normal T cells. Induction of a dendritic AML cell phenotype is associated with an altered chemokine release profile. Detailed characterization of chemokine release should be included in future studies of AML-DC vaccination.