| First Author | Richards JO | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 1 | Pages | 246-52 |
| PubMed ID | 16556890 | Mgi Jnum | J:135679 |
| Mgi Id | MGI:3794258 | Doi | 10.1182/blood-2005-11-4535 |
| Citation | Richards JO, et al. (2006) Tumor growth impedes natural-killer-cell maturation in the bone marrow. Blood 108(1):246-52 |
| abstractText | 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. |
