Down-regulation of signal transducer and activator of transcription 3 improves human acute myeloid leukemia-derived dendritic cell function

Leuk Res. 2013 Jul;37(7):822-8. doi: 10.1016/j.leukres.2013.04.002. Epub 2013 Apr 28.

Abstract

Signal transducer and activator of transcription (STAT) 3 inhibits dendritic cell (DC) differentiation and is constitutively activated in blasts of approximately half of AML patients. We investigated the correlation between STAT3 activity, DC maturation and the ability to stimulate T-cells in primary acute myeloid leukemia (AML)-derived DCs. STAT3 knock-down by shRNAmir increased the ability of AML-DCs to stimulate T-cells. Treatment of AML-DC with arsenic trioxide, but not AG490, JSI-124 or NSC-74859, led to a more mature phenotype and enhanced T-cell stimulation, while having minimal effect on normal DC. We conclude that AML-DCs have improved immunogenicity after reducing STAT3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminosalicylic Acids / pharmacology
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Antineoplastic Agents / pharmacology
  • Arsenic Trioxide
  • Arsenicals / pharmacology
  • Benzenesulfonates / pharmacology
  • Blast Crisis / immunology*
  • Blast Crisis / metabolism
  • Blast Crisis / pathology
  • Blotting, Western
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Down-Regulation
  • Endocytosis / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Lymphocyte Activation / drug effects
  • Oxides / pharmacology
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Tumor Cells, Cultured

Substances

  • Aminosalicylic Acids
  • Antineoplastic Agents
  • Arsenicals
  • Benzenesulfonates
  • NSC 74859
  • Oxides
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Arsenic Trioxide