Xia Liming, Wu Hao, Qian Wenkang
Department of Musculoskeletal Cancer Surgery, Zhejiang Cancer Hospital, Hangzhou 310000, People's Republic of China.
J Bone Oncol. 2018 Jun 25;12:61-64. doi: 10.1016/j.jbo.2018.05.002. eCollection 2018 Sep.
Brain metastasis of osteosarcoma are rare but carry a dismal prognosis. Despite the advances in both systemic immunotherapy and localized radiation, it is still difficult to treat brain metastasis, with less than 12 months of survival from the time of diagnosis for most patients. Currently, there is interest in combining strategies to take advantage of the potential synergy. In this study, the mouse model of metastatic osteosarcoma to brain was used to explore the ability of local radiation and anti-PD-1 blockade to induce beneficial anti-tumor immune responses against distant, unirradiated brain metastatic tumors. Immune markers from the peripheral blood and tumor tissue were analyzed by flow cytometry, real-time PCR and western blot. The combination treatment produced a stronger systemic anti-tumor response than either treatment alone, shown by the reduced tumor burden and larger numbers of cytotoxic CD8 T cells in the unirradiated tumors, indicating an abscopal effect. These data suggested that combination treatment of irradiation with anti-PD-1 immunotherapy can induce abscopal anti-tumor responses and improve both local and distant control.
骨肉瘤脑转移罕见但预后不佳。尽管全身免疫治疗和局部放疗都取得了进展，但脑转移仍难以治疗，大多数患者从诊断时起生存期不到12个月。目前，人们对联合治疗策略以利用潜在协同作用很感兴趣。在本研究中，利用骨肉瘤脑转移小鼠模型来探究局部放疗和抗PD-1阻断诱导针对远处未受照射的脑转移瘤的有益抗肿瘤免疫反应的能力。通过流式细胞术、实时PCR和蛋白质印迹法分析外周血和肿瘤组织中的免疫标志物。联合治疗比单独任何一种治疗产生更强的全身抗肿瘤反应，未受照射肿瘤的肿瘤负荷降低和细胞毒性CD8 T细胞数量增加表明了远隔效应。这些数据表明，放疗与抗PD-1免疫治疗联合可诱导远隔抗肿瘤反应并改善局部和远处控制。
