New insights into the role of T cells in the vicious cycle of bone metastases.
OBJECTIVE
Bone metastases interact with the bone microenvironment. Cancer cells modulate the functions of osteoblasts and osteoclasts to induce new bone formation or bone resorption, leading to secondary stimulation of tumor development. Recent findings suggest the involvement of T cells in this process.


RESULTS
Bone metastatic cancer cells produce factors such as parathyroid hormone-related protein, interleukin-7, and interleukin-8 that can recruit or activate T cells. T cells are involved in bone remodeling and can induce osteoclastic resorption. Bone resorption releases transforming growth factor-beta, however, which could suppress T-cell antitumor immune responses. Bisphosphonate antiresorptive drugs are the approved treatment for solid tumor bone metastases. They have recently been found to activate the cytolytic activity of gammadelta T cells. Thus, inhibitors of transforming growth factor-beta or antiresorptive therapies may be effective enhancers of antitumor immune responses in bone.


CONCLUSIONS
T cells at the site of bone metastases may be functionally suppressed by factors in the bone microenvironment. Instead of acting against tumor cells, they may increase bone resorption, making bone a privileged site for tumor growth.
Fournier
Pierrick G J
PG
Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, Virginia 22908-1419, USA.
Chirgwin
John M
JM
Guise
Theresa A
TA
D001859:Bone Neoplasms / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008213:Lymphocyte Activation; D018448:Models, Immunological; D009362:Neoplasm Metastasis / Q000276:immunology*; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D015851:Interleukin-7; D016209:Interleukin-8; D044162:Parathyroid Hormone-Related Protein