PGE1-Containing Protocols Generate Mature (Leukemia-Derived) Dendritic Cells Directly from Leukemic Whole Blood

Int J Mol Sci. 2019 Sep 17;20(18):4590. doi: 10.3390/ijms20184590.

Abstract

Dendritic cells (DCs) and leukemia-derived DC (DCleu) are potent stimulators of various immunoreactive cells and they play a pivotal role in the (re-) activation of the immune system. As a potential treatment tool for patients with acute myeloid leukemia, we developed and analyzed two new PGE1-containing protocols (Pici-PGE1, Kit M) to generate DC/DCleu ex vivo from leukemic peripheral blood mononuclear cells (PBMCs) or directly from leukemic whole blood (WB) to simulate physiological conditions. Pici-PGE1 generated significantly higher amounts of DCs from leukemic and healthy PBMCs when compared to control and comparable amounts as the already established protocol Pici-PGE2. The proportions of sufficient DC-generation were even higher after DC/DCleu-generation with Pici-PGE1. With Kits, it was possible to generate DCs and DCleu directly from leukemic and healthy WB without induction of blast proliferation. The average amounts of generated DCs and DCleu-subgroups were comparable with all Kits. The PGE1 containing Kit M generated significantly higher amounts of mature DCs when compared to the PGE2-containing Kit K and increased the anti-leukemic-activity. In summary PGE1-containing protocols were suitable for generating DC/DCleu from PBMCs as well as from WB, which reliably (re-) activated immunoreactive cells, improved the overall ex vivo anti-leukemic activity, and influenced cytokine-release-profiles.

Keywords: AML; PGE1; dendritic cells; immunotherapy; leukemia-derived dendritic cells.

MeSH terms

  • Adult
  • Aged
  • Alprostadil / pharmacology*
  • Biomarkers
  • Cell Differentiation / drug effects
  • Cytokines / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects*
  • Female
  • Flow Cytometry
  • Humans
  • Immunomodulation / drug effects
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Picibanil / pharmacology
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Picibanil
  • Alprostadil