Aim: To use inhibition of colony-stimulating factor-1 receptor (CSF-1R) to target tumor-associated macrophages (TAMs) and improve the efficacy of radiotherapy in glioblastoma (GBM). Materials and Methods: The CSF-1R inhibitor BLZ-945 was used to examine the impact of CSF-1R inhibition on M2 polarization in vitro. Using an orthotopic, immunocompetent GBM model, mice were treated with vehicle, RT, BLZ-945, or RT plus BLZ-945. Results: BLZ-945 reduced M2 polarization in vitro. BLZ-945 alone did not improve median overall survival (mOS=29 days) compared to control mice (mOS=27 days). RT improved survival (mOS=45 days; p=0.02), while RT plus BLZ-945 led to the longest survival (mOS=not reached; p=0.005). Resected tumors had a relatively large population of M2 TAMs in GBM at baseline, which was increased in response to RT. BLZ-945 reduced RT-induced M2 infiltration. Conclusion: Inhibition of CSF-1R improved response to RT in the treatment of GBM and may represent a promising strategy to improve RT-induced antitumor immune responses.

中文翻译：

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抑制集落刺激因子 1 受体可增强胶质母细胞瘤放疗的疗效并减少免疫抑制

目的：通过抑制集落刺激因子-1受体（CSF-1R）来靶向肿瘤相关巨噬细胞（TAM），提高胶质母细胞瘤（GBM）放疗的疗效。材料和方法：使用 CSF-1R 抑制剂 BLZ-945 检测 CSF-1R 抑制对体外 M2 极化的影响。使用原位免疫活性 GBM 模型，用载体、RT、BLZ-945 或 RT 加 BLZ-945 治疗小鼠。结果：BLZ-945 降低体外 M2 极化。与对照小鼠（mOS = 27 天）相比，单独使用 BLZ-945 并不能改善中位总生存期（mOS = 29 天）。RT 提高了生存率（mOS=45 天；p=0.02），而 RT 加 BLZ-945 则实现了最长的生存期（mOS=未达到；p=0.005）。基线时，切除的肿瘤在 GBM 中具有相对较多的 M2 TAM 群体，随着放疗的反应而增加。BLZ-945 减少 RT 诱导的 M2 浸润。结论：抑制 CSF-1R 可以改善 GBM 治疗中对放疗的反应，并且可能是改善放疗诱导的抗肿瘤免疫反应的一种有前景的策略。