Tumor growth impedes natural-killer-cell maturation in the bone marrow.
Journal: 2007/August - Blood
ISSN: 0006-4971
Abstract:
Natural-killer (NK)-cell dysfunction and IFN-gamma deficiencies have been associated with increased incidence of both malignancy and infection. The immunologic 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-gamma production but seemingly normal cytotoxicity. T cells are not involved in this NK maturation arrest, because T-cell depletion did not restore NK-cell development. Moreover, the extent of tumor-cell infiltration into the bone marrow does not correlate with defective NK maturation. Interestingly, the defect was associated with a significant reduction in the IL-15Ralpha+ cells in the non-T, non-NK compartment of bone marrow cells and restored by overexpression 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.
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Blood 108(1): 246-252

Tumor growth impedes natural-killer-cell maturation in the bone marrow

From the Division of Cancer Immunology, Department of Pathology; and the Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus.
Reprints: Yang Liu, Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210; e-mail: ude.uso.rtcdem@3-uil.
Reprints: Yang Liu, Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210; e-mail: ude.uso.rtcdem@3-uil.
Received 2005 Nov 16; Accepted 2006 Feb 20.

Abstract

Natural-killer (NK)-cell dysfunction and IFN-γ deficiencies have been associated with increased incidence of both malignancy and infection. The immunologic 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-γ production but seemingly normal cytotoxicity. T cells are not involved in this NK maturation arrest, because T-cell depletion did not restore NK-cell development. Moreover, the extent of tumor-cell infiltration into the bone marrow does not correlate with defective NK maturation. Interestingly, the defect was associated with a significant reduction in the IL-15Rα cells in the non-T, non-NK compartment of bone marrow cells and restored by overexpression 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. (Blood. 2006;108:246-252)

Abstract
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Acknowledgments

We thank Dr Ou Li for technical assistance and Lynde Shaw for editorial assistance.

Acknowledgments

Notes

Prepublished online as Blood First Edition Paper, March 23, 2006; DOI 10.1182/blood-2005-11-4535.

Supported by National Institutes of Health grants P01CA95426, R01 CA58033, and T32CA090223.

The online version of this article contains a data supplement.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

Notes
Prepublished online as Blood First Edition Paper, March 23, 2006; DOI 10.1182/blood-2005-11-4535.
Supported by National Institutes of Health grants P01CA95426, R01 CA58033, and T32CA090223.
The online version of this article contains a data supplement.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

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