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Blood, 1 July 2006, Vol. 108, No. 1, pp. 246-252. Prepublished online as a Blood First Edition Paper on March 23, 2006; DOI 10.1182/blood-2005-11-4535. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-11-4535v1 108/1/246    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Richards, J. Articles by Liu, Y. Search for Related Content PubMed PubMed Citation Articles by Richards, J. Articles by Liu, Y. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 16, 2005 Accepted February 20, 2006 Tumor growth impedes natural-killer cell maturation in the bone marrow John Richards, Chang Xing, Bradley W Blaser, Michael A Caligiuri, Pan Zheng, and Yang Liu* Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio, USA Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio, USA * Corresponding author; email: yang.liu{at}medctr.osu.edu. NK cell dysfunction and IFN-gamma deficiencies have been associated with increased incidence of both malignancy and infection. The immunological basis of NK cell defects in cancer-bearing hosts has not been extensively studied. Here we demonstrate that multiple lineages of tumors, including thymoma, breast cancer, colon cancer and melanoma cell lines interrupt functional maturation during NK cell development in the bone marrow. The immature NK cells in the periphery of tumor-bearing mice had impaired IFN- production but seemingly normal cytotoxicity. T cells are not involved in this NK maturation arrest as T cell depletion did not restore NK cell development. Moreover, the extent of tumor cell-infiltration into bone marrow does not correlate with the defective NK maturation. Interestingly, the defect was associated with a significant reduction in the IL-15R-positive cells in the non-T, non-NK compartment of bone marrow cells and restored by over expression of IL-15. Our data demonstrate that tumor growth can impede functional maturation of NK cells, most likely by interrupting the requisite IL-15 signaling pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Romagne, P. Andre, P. Spee, S. Zahn, N. Anfossi, L. Gauthier, M. Capanni, L. Ruggeri, D. M. Benson Jr, B. W. Blaser, et al. Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells Blood, September 24, 2009; 114(13): 2667 - 2677. [Abstract] [Full Text] [PDF] Y. M. El-Sherbiny, J. L. Meade, T. D. Holmes, D. McGonagle, S. L. Mackie, A. W. Morgan, G. Cook, S. Feyler, S. J. Richards, F. E. Davies, et al. The Requirement for DNAM-1, NKG2D, and NKp46 in the Natural Killer Cell-Mediated Killing of Myeloma Cells Cancer Res., September 15, 2007; 67(18): 8444 - 8449. [Abstract] [Full Text] [PDF] A Plonquet, C Haioun, J-P Jais, A-L Debard, G Salles, M-C Bene, P Feugier, C Rabian, O Casasnovas, M Labalette, et al. Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2 3 diffuse large B-cell lymphoma Ann. Onc., July 1, 2007; 18(7): 1209 - 1215. [Abstract] [Full Text] [PDF]

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