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Cancer Res. 2011 Jul 15;71(14):4799-808. doi: 10.1158/0008-5472.CAN-10-3922. Epub 2011 May 20.

CD8+ T cells regulate bone tumor burden independent of osteoclast resorption.

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1
Department of Orthopedics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Erratum in

  • Cancer Res. 2012 Jan 15;72(2):568.

Abstract

Blockade of osteoclast (OC) activity efficiently decreases tumor burden as well as associated bone erosion in immune-compromised animals bearing human osteolytic cancers. In this study, we showed that modulation of antitumor T-cell responses alters tumor growth in bone, regardless of OC status, by using genetic and pharmacologic models. PLCγ2(-/-) mice, with dysfunctional OCs and impaired dendritic cell (DC)-mediated T-cell activation, had increased bone tumor burden despite protection from bone loss. In contrast, Lyn(-/-) mice, with more numerous OCs and a hyperactive myeloid population leading to increased T-cell responses, had reduced tumor growth in bone despite enhanced osteolysis. The unexpected tumor/bone phenotype observed in PLCγ2(-/-) and Lyn(-/-) mice was transplantable, suggesting the involvement of an immune component. Consistent with this hypothesis, T-cell activation diminished skeletal metastasis whereas T-cell depletion enhanced it, even in the presence of zoledronic acid, a potent antiresorptive agent. Importantly, injection of antigen-specific wild-type cytotoxic CD8(+) T cells in PLCγ2(-/-) mice or CD8(+) T-cell depletion in Lyn(-/-) mice normalized tumor growth in bone. Our findings show the important contribution of CD8(+) T cells in the regulation of bone metastases regardless of OC status, thus including T cells as critical regulators of tumor growth in bone.

PMID:
21602433
PMCID:
PMC3138866
DOI:
10.1158/0008-5472.CAN-10-3922
[Indexed for MEDLINE]
Free PMC Article

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