title: CD8+ T cells regulate bone tumor burden independent of osteoclast resorption.
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.
authors: Department of Orthopedics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Kaihua
authors: K
authors: Zhang
authors: Seokho
authors: S
authors: Kim
authors: Viviana
authors: V
authors: Cremasco
authors: Angela C
authors: AC
authors: Hirbe
authors: Lynne
authors: L
authors: Collins
authors: David
authors: D
authors: Piwnica-Worms
authors: Deborah V
authors: DV
authors: Novack
authors: Katherine
authors: K
authors: Weilbaecher
authors: Roberta
authors: R
authors: Faccio
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