Bone metastases are devastating complications of cancer. They are particularly common in prostate cancer (PCa), represent incurable disease, and are refractory to immunotherapy. We seek to define distinct features of the bone marrow (BM) microenvironment by analyzing single cells from bone metastatic prostate tumors, involved BM, uninvolved BM, and BM from cancer-free, orthopedic patients, and healthy individuals. Metastatic PCa is associated with multifaceted immune distortion, specifically exhaustion of distinct T cell subsets, appearance of macrophages with states specific to PCa bone metastases. The chemokine CCL20 is notably overexpressed by myeloid cells, as is its cognate CCR6 receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic PCa bone metastases restores T cell reactivity and significantly prolongs animal survival. Comparative high-resolution analysis of PCa bone metastases shows a targeted approach for relieving local immunosuppression for therapeutic effect.

骨转移是癌症的毁灭性并发症。它们在前列腺癌 (PCa) 中特别常见，代表无法治愈的疾病，并且免疫疗法难以治疗。我们试图通过分析来自骨转移性前列腺肿瘤、受累的 BM、未受累的 BM 和来自无癌症、骨科患者和健康个体的 BM 的单个细胞来定义骨髓 (BM) 微环境的不同特征。转移性 PCa 与多方面的免疫扭曲有关，特别是不同 T 细胞亚群的耗竭、具有 PCa 骨转移特异性状态的巨噬细胞的出现。趋化因子 CCL20 显着被骨髓细胞过度表达，其在 T 细胞上的同源 CCR6 受体也是如此。在具有同系 PCa 骨转移的小鼠中破坏 CCL20-CCR6 轴可恢复 T 细胞反应性并显着延长动物存活时间。PCa 骨转移的比较高分辨率分析显示了一种用于缓解局部免疫抑制以获得治疗效果的靶向方法。