title: Cytokine upregulation of the antigen presenting function of acute myeloid leukemia cells.
abstract: Acute myeloid leukemia (AML) cells are malignant counterparts of normal myeloid pathway progenitors. Myeloid progenitors differentiate into professional antigen presenting cells (APC) under the essential influence of GM-CSF along with additional cytokines. Twelve cases of human AML were tested for ability to be differentiated toward a professional APC phenotype in short-term culture with addition of GM-CSF and the following recombinant proteins: TNFalpha, IL-4, CD40 ligand, Flt3 ligand and SCF. Significant upregulation of CD80 (B7-1) and enhancement of alloantigen presentation was seen with the addition of GM-CSF and TNFalpha alone or with additional cytokines. The combination of GM-CSF and TNFalpha, either alone or in combination with an additional cytokine, resulted in enhancing alloantigen presentation by at least two-fold over the media control group in 10/12 patients studied, and resulted in CD80 expression of greater than 15% in 11/12 patients studied. In AML cultures with GM-CSF and TNFalpha, coexpression of CD80 and either CD34 or an aberrant surface marker (CD56) was seen. In one case, sorted CD80, cells retained a characteristic cytogenetic marker and CD34 expression, proving their derivation from an AML precursor. These studies verify other reports of in vitro differentiation of human AML precursors into enhanced APC, suggesting that this phenomenon could be utilized for immunotherapy strategies aimed at enhancing presentation of leukemia antigens to T cells.
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Boyer
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
authors.forename: R A
authors.initials: RA
authors.lastname: Bray
authors.forename: T
authors.initials: T
authors.lastname: Unangst
authors.forename: T S
authors.initials: TS
authors.lastname: Johnson
authors.forename: C
authors.initials: C
authors.lastname: Phillips
authors.forename: I
authors.initials: I
authors.lastname: Jurickova
authors.forename: E F
authors.initials: EF
authors.lastname: Winton
authors.forename: A M
authors.initials: AM
authors.lastname: Yeager
mesh_terms: D000208:Acute Disease; D000328:Adult; D017951:Antigen Presentation / Q000187:drug effects*; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000235:genetics; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D023201:CD40 Ligand; D019002:CD56 Antigen / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015847:Interleukin-4 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology; D019089:Stem Cell Factor / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D018122:B7-1 Antigen; D019002:CD56 Antigen; D016207:Cytokines; D007519:Isoantigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D023201:CD40 Ligand; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor