Gnoni Antonio, Brunetti Oronzo, Longo Vito, Calabrese Angela, Argentiero Antonel-la, Calbi Roberto, Solimando Antonio Giovanni, Licchetta Antonella
Medical Oncology Unit, "S. Cuore di Gesù" Hospital, Gallipoli, Italy.
Medical Oncology Unit, National Cancer Research Centre, IRCCS IstitutoTumori "Giovanni Paolo II", Bari, Italy.
Oncotarget. 2020 Jan 28;11(4):480-487. doi: 10.18632/oncotarget.27439.
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.
骨免疫学这一术语大约在二十年前被创造出来，用于确定骨微环境与免疫系统在包括癌症在内的生理和病理活动中的严格相互作用。有几种分子参与了骨微环境、免疫细胞和癌细胞之间的复杂相互作用。核因子-κB受体激活剂（RANK）/RANK配体（RANKL）/骨保护素（OPG）通路在骨细胞/癌症相互作用中起着关键作用，随后会导致免疫系统控制失效、骨质破坏、疗效抑制和转移结果。骨与免疫系统之间的双向相互作用可能成为抗癌药物的潜在靶点。多项研究证明了骨靶向治疗（如双膦酸盐和RANKL拮抗剂地诺单抗）具有直接抗癌作用并能提高生存率。相反，初步数据表明，全身性抗癌药物可通过免疫调节活性产生抗骨吸收作用，例如前列腺癌中的新一代抗雄激素药物（阿比特龙）。所有这些数据都可能为癌症治疗中联合骨治疗、免疫治疗和靶向治疗提供未来的理论依据。
