title: Down-regulation of signal transducer and activator of transcription 3 improves human acute myeloid leukemia-derived dendritic cell function.
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.
authors.affiliation: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Brady
authors.forename: Austin
authors.initials: A
authors.lastname: Miller
authors.forename: Sheila N
authors.initials: SN
authors.lastname: Sait
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Ford
authors.forename: Hans
authors.initials: H
authors.lastname: Minderman
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Lee
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology; D001752:Blast Crisis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000636:Aminosalicylic Acids; D000970:Antineoplastic Agents; D001152:Arsenicals; D001557:Benzenesulfonates; C520337:NSC 74859; D010087:Oxides; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D000077237:Arsenic Trioxide