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

2006; Elsevier BV; Volume: 108; Issue: 1 Linguagem: Inglês

10.1182/blood-2005-11-4535

1528-0020

John O. Richards, Xing Chang, Bradley W. Blaser, Michael A. Caligiuri, Pan Zheng, Yang Liu,

Hematopoietic Stem Cell Transplantation

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)