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Immunobiology

Cytokine upregulation of the antigen presenting function of acute myeloid leukemia cells

Leukemia volume 14, pages 412–418 (2000)Cite this article

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: TNFα, 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 TNFα alone or with additional cytokines. The combination of GM-CSF and TNFα, 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 TNFα, 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.

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Acknowledgements

We wish to thank Dr Elaine Thomas (Immunex, Seattle, WA) for providing the trimeric soluble CD40 ligand and for her encouragement. This work was supported by the Egleston Celebrity Classic to Beat Leukemia, Atlanta, Georgia; and Amgen Corporation, Thousand Oaks, California.

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Authors and Affiliations

  1. Department of Pediatrics, Emory University, Atlanta, Georgia, USA

    MW Boyer, T Unangst, TS Johnson, I Jurickova & AM Yeager

  2. Department of Medicine, Emory University, Atlanta, Georgia, USA

    EK Waller, EF Winton & AM Yeager

  3. Department of Pathology, Emory University, Atlanta, Georgia, USA

    RA Bray & C Phillips

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  1. MW Boyer
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Boyer, M., Waller, E., Bray, R. et al. Cytokine upregulation of the antigen presenting function of acute myeloid leukemia cells. Leukemia 14, 412–418 (2000). https://doi.org/10.1038/sj.leu.2401685

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