Journal
BLOOD
Volume 108, Issue 1, Pages 246-252Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-11-4535
Keywords
-
Categories
Funding
- NCI NIH HHS [P01CA95426, R01 CA58033, T32CA090223] Funding Source: Medline
Ask authors/readers for more resources
Natural-killer (NK)-cell dysfunction and IFN-gamma deficiencies have been associated with increased incidence of both malignancy and infection. The immunologic basis of INK-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 INK cells in the periphery of tumor-bearing mice had impaired IFN-gamma production but 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 INK maturation. Interestingly, the defect was associated with a significant reduction in the IL-15R alpha(+) 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 INK cells, most likely by interrupting the requisite IL-15 signaling pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available