Dendritic Cells as Double-Agents for Breast Tumor Pre-Metastatic Bone Disease Establishment

Pre-metastatic niche formation at distant sites can be initiated by the primary tumor through “education” of non tumoral cells present in the primary cancerous niche. Among other participants, immune cells and their secreted factors can boost the successful seeding of the distant disease. Accordingly, we showed that RANKL production by breast tumor-primed T cells is required for development of bone metastasis. Pro-osteoclastogenic tumor-specific RANKL+ T cells were shown as messengers from the periphery to the bone marrow, where they alter bone turnover homeostasis in favour of osteoclasts and before tumor colonization. Pre-metastatic T cell-mediated osteolytic disease generates a rich environment that will allow further colonization of the bone cavity by the metastatic clones. Once initial seeding of the bone tissue is achieved, tumor cells can continue the osteolytic process on their own, feeding themselves through the vicious cycle established. More recently, we explored the contribution of dendritic cells for the maintenance of such tumor-specific T cells activity for bone marrow pre-metastatic niche formation. Indeed, dendritic cells can act as both an APC for RANKL+ tumor-specific T cells activation and as an osteoclast-like cell, amplifying the pre-osteolytic phenomena. Here, we discuss the potential differentiation of DCs into OCs for bone pre osteolytic disease establishment, either directly or through the maintenance of RANKL+ T cell inside the bone marrow. The understanding of the cellular and molecular interactions that build the bone pre-metastatic niche can be directed towards prevention and/or treatment of metastatic bone disease.