Immune system and bone microenvironment: rationale for targeted cancer therapies

// Gnoni Antonio 1 , Brunetti Oronzo 2 , Longo Vito 3 , Calabrese Angela 4 , Argentiero Antonel-la 2 , Calbi Roberto 5 , Solimando Antonio Giovanni 6 and Licchetta Antonella 1 1 Medical Oncology Unit, “S. Cuore di Gesù” Hospital, Gallipoli, Italy 2 Medical Oncology Unit, National Cancer Research Centre, IRCCS IstitutoTumori “Giovanni Paolo II”, Bari, Italy 3 Radiology Unit, National Cancer Research Centre, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy 4 Medical ThoracicOncology Unit, IRCCS IstitutoTumori “Giovanni Paolo II”, Viale Orazio Flacco, Bari, Italy 5 Radiology Unit, Ente Ecclesiastico “F. Miulli” Hospital, Acquaviva delle Fonti, Italy 6 Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari Medical School, Bari, Italy Correspondence to: Gnoni Antonio, email: drgnoni.antonio@libero.it Keywords: antiandrogens; bisphosphonates; bone niche; immune system; osteoimmunology Received: October 09, 2019 Accepted: December 31, 2019 Published: January 28, 2020 ABSTRACT Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator of NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.