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

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.

journal_name

Blood

journal_title

Blood

authors

Richards JO,Chang X,Blaser BW,Caligiuri MA,Zheng P,Liu Y

doi

10.1182/blood-2005-11-4535

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

246-52

issue

1

eissn

0006-4971

issn

1528-0020

pii

2005-11-4535

journal_volume

108

pub_type

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