| First Author | Zhang K | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 14 | Pages | 4799-808 |
| PubMed ID | 21602433 | Mgi Jnum | J:174081 |
| Mgi Id | MGI:5051867 | Doi | 10.1158/0008-5472.CAN-10-3922 |
| Citation | Zhang K, et al. (2011) CD8+ T Cells Regulate Bone Tumor Burden Independent of Osteoclast Resorption. Cancer Res 71(14):4799-808 |
| abstractText | 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. PLCgamma2(-/-) 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 PLCgamma2(-/-) 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 PLCgamma2(-/-) 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. Cancer Res; 71(14); 4799-808. (c)2011 AACR. |
