Potential of Targeting Bone Metastases with Immunotherapies

Cancer metastases cause high morbidity and mortality in patients. Bone metastases are most common in breast and prostate cancer, but they are also observed in many other cancers such as lung and renal cancer and melanoma [1]. In breast cancer the formation of metastases depends on the tumor subtype, and the major site for metastasis is the skeleton [2]. Patients with bone metastases have a 5-year survival rate of only 21% and a median survival time of 3 years. Prostate cancer is currently described as a bone disease due to high incidence of skeletal metastases. In prostate cancer patients with bone metastases, the 5-year survival rate is about 30% and the median survival time is 3 years [3]. Metastatic cancer patients are treated with conventional cancer therapies that are usually ineffective against bone metastases. Tumor-induced bone loss can also be treated with bone-targeting therapies. Bone marrow is an important immune organ that contains many immune cells, such as myeloid-derived suppressor cells, T cells, B cells and natural killer cells, and it is a cytokine rich microenvironment [4-6]. Immune cells can regulate many aspects of formation and growth of bone metastases [4]. Bone marrow is an immunosuppressive microenvironment, and immune suppressive cells in bone may promote tumor progression [5]. On the contrary, cytotoxic T cells and NK cells can be activated by immunomodulators to mediate anti-tumor effects. In addition, immune cells directly interact with bone cells, promoting tumor-induced effects on bone [6].