title: Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.
abstract: 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.
authors.affiliation: Division of Experimental Therapeutics, Breast Cancer Program, Istituto Europeo di Oncologia, Via Ripamonti 435, 20133 Milano, Italy. Electronic address: carmen.criscitiello@ieo.it.
authors.forename: Carmen
authors.initials: C
authors.lastname: Criscitiello
authors.affiliation: Division of Experimental Therapeutics, Breast Cancer Program, Istituto Europeo di Oncologia, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Viale
authors.affiliation: Division of Experimental Therapeutics, Breast Cancer Program, Istituto Europeo di Oncologia, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gelao
authors.affiliation: Division of Experimental Therapeutics, Breast Cancer Program, Istituto Europeo di Oncologia, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Department of Breast Oncology, National Cancer Institute "Fondazione Pascale", Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: De Laurentiis
authors.affiliation: Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Napoli, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.affiliation: Department of Advanced Medical Sciences, Operative Unit of General Surgery and Transplants, University of Naples Federico II, Napoli, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Santangelo
authors.affiliation: Division of Experimental Therapeutics, Breast Cancer Program, Istituto Europeo di Oncologia, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Division of Experimental Therapeutics, Breast Cancer Program, Istituto Europeo di Oncologia, Via Ripamonti 435, 20133 Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001847:Bone Diseases / Q000276:immunology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary; D016723:Bone Remodeling / Q000276:immunology*; D001862:Bone Resorption / Q000276:immunology*; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism*; D004002:Clodronic Acid / Q000494:pharmacology; D000069448:Denosumab; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000494:pharmacology; D007107:Immune System; D010010:Osteoclasts / Q000187:drug effects* / Q000276:immunology; D053244:Osteoprotegerin / Q000187:drug effects / Q000378:metabolism; D000077268:Pamidronate; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D004002:Clodronic Acid; D000069448:Denosumab; D000077211:Zoledronic Acid; D000077268:Pamidronate; D000077557:Ibandronic Acid
keywords: Bone; Cancer; Immune system; Osteoimmunology; RANK