Synergistic effect of Toll-like receptor 4 and 7/8 agonists is necessary to generate potent blast-derived dendritic cells in Acute Myeloid Leukemia

Leuk Res. 2012 Sep;36(9):1193-9. doi: 10.1016/j.leukres.2012.04.007. Epub 2012 May 10.

Abstract

Leukemic cells from AML patients can be differentiated to dendritic cells (DCs). Such DCs have potential for immunotherapy of patients. Blasts from 15 AML patients were differentiated into DCs and matured by different TLR agonists. We could generate AML-DCs from 73% of patients mostly with M4 or M5 subtypes. The DC recoveries ranged from 28% to 50%. The results showed that concomitant use of TLR4 and TLR7/8 agonists induced proficient DCs. Therefore, a combination of TLR4 and 7/8 agonists can be considered as an appropriate maturation cocktail for AML-DC production in order to use in the immunotherapy of AML patients.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blast Crisis / immunology
  • Blast Crisis / pathology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / drug effects*
  • Dendritic Cells / pathology
  • Dendritic Cells / physiology
  • Drug Synergism
  • Female
  • Humans
  • Imidazoles / pharmacology*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology*
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Poly I-C / pharmacology*
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 8 / agonists
  • Young Adult

Substances

  • Imidazoles
  • Lipopolysaccharides
  • TLR4 protein, human
  • TLR7 protein, human
  • TLR8 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Poly I-C
  • resiquimod