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

  • Miroslaw J. Szczepanski
  • Marta Szajnik
  • Ann Welsh
  • Kenneth A. Foon
  • Theresa L. Whiteside
  • Michael BoyiadzisEmail author
Original Article

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.

Keywords

Acute myeloid leukemia Natural killer cells Activating receptors NCRs NKG2D Interleukin -15 

Notes

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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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Miroslaw J. Szczepanski
    • 1
    • 2
  • Marta Szajnik
    • 1
  • Ann Welsh
    • 1
  • Kenneth A. Foon
    • 1
  • Theresa L. Whiteside
    • 1
    • 3
  • Michael Boyiadzis
    • 1
    Email author
  1. 1.Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Cancer Institute University of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Departments of Clinical Immunology and OtolaryngologyPoznan University of Medical SciencesPoznanPoland
  3. 3.Department of PathologyUniversity of Pittsburgh School of MedicinePittsburghUSA

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