Beyond the vicious cycle: The role of innate osteoimmunity, automimicry and tumor-inherent changes in dictating bone metastasis

Bone metastasis is a fatal consequence of a subset of solid malignancies that fail to respond to conventional therapies. While a myriad of factors contribute to osteotropism and disseminated cell survival and outgrowth in bone, efforts to inhibit tumor cell growth in the bone-metastatic niche have largely relied on measures that disrupt the bi-directional interactions between bone resident and tumor cells. However, the targeting of isolated stromal interactions has proven ineffective to date in inhibiting bone-metastatic progression and patient mortality. Osteoimmune regulation is now emerging as a critical determinant of metastatic growth in the bone microenvironment. While this has highlighted the importance of innate immune populations in dictating the temporal development of overt bone metastases, the osteoimmunological processes that underpin tumor cell progression in bone remain severely underexplored. Along with tumor-intrinsic alterations that occur specifically within the bone microenvironment, innate osteoimmunological crosstalk poses an exciting area of future discovery and therapeutic development. Here we review current knowledge of the unique exchange that occurs between bone resident cells, innate immune populations and tumor cells that leads to the establishment of a tumor-permissive milieu.