Emerging roles for myeloid immune cells in bone metastasis

Metastasis, especially bone metastasis, is a major cause of cancer-related deaths, which is associated with long-term pain due to skeletal-related events and poor quality of life. Tumor cells alter the bone microenvironment through aberrant activation of osteoclasts and osteoblasts which induces bone osteolysis and release of growth factors leading to cancer growth. Though this phenomenon has been well characterized, bone-targeted therapies have shown little improvement in patient survival. Recent evidence indicates a growing appreciation for the complex bone environment, in addition to bone-remodeling stromal cells, which includes an abundance of myeloid immune cells that can either protect against or contribute to the progression of the disease within the bone cavity. Additionally, myeloid cells are recruited into primary tumor sites, where they promote development of the pre-metastatic niche and also can regulate tumor progression within the tumor-bone microenvironment through a milieu of complex mechanisms and involving heterogeneous myeloid populations. In this review, we have highlighted the complex roles of myeloid immunity in bone metastasis and hope to bring attention to the potential of novel immunotherapeutic interventions for the elimination of bone metastasis.