Immune regulation of bone XXXX .

@entity1 @entity5 @entity0 @entity3
@entity3 to bone occur in about 70% of @entity1 with metastatic prostate and @entity0 . Unfortunately, bone metastases result in significant morbidity and mortality and treatment options are limited. Thus, significant effort has focused on understanding the mechanisms that @entity5 dissemination to bone. Bone metastases are typically characterized by a self-perpetuating 'vicious' cycle wherein @entity5 cells and bone-resorbing cells (osteoclasts) are locked in a cycle that leads to osteoclast-driven bone destruction and the release of bone-stored factors that in turn stimulate @entity5 cell proliferation and survival. To break this 'vicious' cycle, potent antiresorptive agents such as zoledronic acid (ZOL) have been used. However, in the clinical setting, ZOL failed to improve the overall survival of @entity5 @entity1 even though it inhibited osteoclast resorptive activity. Thus, other cells in addition to osteoclasts are likely involved in modulating @entity5 growth in the bone. The immune system has the ability to eliminate @entity5 cells. Nevertheless, @entity5 cells can acquire the ability to escape immune control. Our recent observations indicated that a decline in the ability of the immune cells to recognize and kill the @entity5 drives @entity5 dissemination to bone even when osteoclasts are inhibited by potent antiresorptive agents. This review focuses on the antitumor and protumor effects of various immune cell populations involved in the bone metastatic process. We also discuss strategies to enhance antitumor immune responses and bypass @entity5 immune resistance.
