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Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors

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Abstract

Interleukin-15 (IL-15) has a major role in NK-cell homeostasis. Modulation of the relative frequency and expression intensity of the NK-cell receptors by IL-15 may increase NK cell-mediated cytotoxicity in cancer patients. We investigated the receptor repertoire and measured NK-cell activity in newly diagnosed AML patients and evaluated the ex vivo effects of IL-15. The expression of the activating NK cell receptors was significantly decreased in the AML patients compared to that in NK cells of healthy donors. When NK cells obtained from AML patients were cultured with IL-15, expression of the activating receptors was significantly upregulated compared to pre-culture levels. Concomitantly, cytotoxic activity of NK cells against autologous leukemic blasts increased following IL-15 stimulation. This IL-15 induced increase in activity was blocked by neutralizing antibodies specific for the NK cell activating receptors. These pre-clinical data support the future use of IL-15 for NK cell- based therapies for AML patients.

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Acknowledgments

This article was supported in part by Production Assistance for Cellular Therapies (PACT) under contract N01-HB-37165 from the NHLBI (TLW, MS), The Mario Lemieux Foundation (MB) and PO1-CA109688 from the NCI (TLW).

Conflict of interest statement

All authors agree with the contents of the manuscript and all authors declare that they have no conflict of interest.

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Author notes

  1. Miroslaw J. Szczepanski

    Present address: Departments of Clinical Immunology and Otolaryngology, Poznan University of Medical Sciences, 61-701, Poznan, Poland

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5150 Centre Avenue, Suite 572, Pittsburgh, PA, 15232, USA

    Miroslaw J. Szczepanski, Marta Szajnik, Ann Welsh, Kenneth A. Foon, Theresa L. Whiteside & Michael Boyiadzis

  2. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Theresa L. Whiteside

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  1. Miroslaw J. Szczepanski
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  2. Marta Szajnik
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  3. Ann Welsh
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  5. Theresa L. Whiteside
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Correspondence to Michael Boyiadzis.

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Szczepanski, M.J., Szajnik, M., Welsh, A. et al. Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors. Cancer Immunol Immunother 59, 73–79 (2010). https://doi.org/10.1007/s00262-009-0724-5

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  • DOI: https://doi.org/10.1007/s00262-009-0724-5

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