دورية أكاديمية
CD8+ T Cells Regulate Bone Tumor Burden Independent of Osteoclast Resorption.
| العنوان: | CD8+ T Cells Regulate Bone Tumor Burden Independent of Osteoclast Resorption. |
|---|---|
| المؤلفون: | Zhang, Kaihua1, Kim, Seokho1, Cremasco, Viviana1, Hirbe, Angela C.2, Novack, Deborah V.3, Weilbaecher, Katherine2, Faccio, Roberta1 faccior@wustl.edu |
| المصدر: | Cancer Research. Jul2011, Vol. 71 Issue 14, p4799-4808. 10p. |
| مصطلحات موضوعية: | *BONE tumors, *BONE cancer, *OSTEOCLASTS, *BONE cells, *DENDRITIC cells, *T cells |
| مستخلص: | 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. Cancer Res; 71(14); 4799-808. ©2011 AACR. [ABSTRACT FROM AUTHOR] |
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