Crosstalk between bone niche and immune system: Osteoimmunology signaling as a potential target for cancer treatment

- Osteoimmunology studies the crosstalk between skeletal and immune systems.
- RANK/RANKL/OPG signaling is essential for osteoclastogenesis, bone remodeling, immune system development and regulation.
- Cancer cells evade immunosurveillance and the bone often harbors DTCs against anticancer therapy and immune response.
- Besides being effective in preventing and treating SREs, bisphosphonates exert direct anti-tumor effects.
- The molecular crosstalk between immune and skeletal systems could be targeted with new therapeutic strategies.

There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called “osteoimmunology”.The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival.