Tumor Growth Impedes Natural-killer-cell Maturation in the Bone Marrow.
From: Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA.
Blood
- Publish Date: Jul 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 1
- Pages: 246-52
- Medium: Print
- Language: English
- Citation (JAMA): Richards John O, Chang Xing, Blaser Bradley W, et al. Tumor Growth Impedes Natural-killer-cell Maturation in the Bone Marrow.. Blood Jul 2006;108:246-52
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.
Mesh Headings (Keywords): Animals, Bone Marrow, Cell Differentiation, Cell Line, Tumor, Cytotoxicity, Immunologic, Humans, Interferon Type II, Interleukin-15, Killer Cells, Natural, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neoplasm Transplantation, Neoplasms, Tumor Escape, Xenograft Model Antitumor Assays
Check for Full Text / PubMed Unique Identifier (PMID): 16556890
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