Abstract
Immunotherapies provide a potential treatment option for currently incurable bone metastases. Bone marrow is an important secondary lymphoid organ with a unique immune contexture. Even at non-disease state immune cells and bone cells interact with each other, bone cells supporting the development of immune cells and immune cells regulating bone turnover. In cancer, tumor cells interfere with this homeostatic process starting from formation of pre-metastatic niche and later supporting growth of bone metastases. In this review, we introduce a novel concept osteoimmuno-oncology (OIO), which refers to interactions between bone, immune and tumor cells in bone metastatic microenvironment. We also discuss therapeutic opportunities of targeting immune cells in bone metastases, and associated efficacy and safety concerns.
Highlights
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This has led to classification of tumors into the ‘hot’ or ‘inflamed’ type when they have a high number of immune cells in the tumor microenvironment (TME), typically resulting in a better response rate to immunotherapies [4]
The uniqueness of the TME becomes especially challenging when cancer forms metastasis to distant organs that each have unique properties. This uniqueness is gained during complicated events of overlapping processes in the metastatic progression [13] that start by tumor cells changing their properties through an epithelial-tomesenchymal transition (EMT) [14,15], allowing them to leave the primary tumor, entera new TME, and modulate the new TME to allow the growth of secondary tumors called metastases
Summary
Many decades have been spent on studying and understanding unique aspects of TME [10,11,12]. Osteoblastic bone metastases induce formation of pathologic new bone, and they are common in prostate cancer. Better understanding and consideration of the metastatic TME in bone would allow to develop novel therapies that would be effective in bone metastases, which to date remain incurable. In light of the above, we would like to propose a novel osteoimmuno-oncology (OIO) approach when developing immuno-oncology compounds for treating bone metastases (Figure 1). This means that all three aspects, bone cell interactions with immune cells (osteoimmunology), immune cell interactions with tumor cells (immuno-oncology), and tumor cell interactions with bone cells, would be considered when developing more effective compounds for patients with the currently incurable bone metastases. We discuss the immunological effects of emerging therapies used in bone metastatic patients and future remarks in this field
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