Nearly half of melanoma patients develop brain metastases during the course of their disease. Despite advances in both localized radiation and systemic immunotherapy, brain metastases remain difficult to treat, with most patients surviving less than 5 months from the time of diagnosis. While both treatment regimens have individually shown considerable promise in treating metastatic melanoma, there is interest in combining these strategies to take advantage of potential synergy. In order to study the ability of local radiation and anti-PD-1 immunotherapy to induce beneficial anti-tumor immune responses against distant, unirradiated tumors, we used two mouse models of metastatic melanoma in the brain, representing BRAF mutant and non-mutant tumors. Combination treatments produced a stronger systemic anti-tumor immune response than either treatment alone. This resulted in reduced tumor growth and larger numbers of activated, cytotoxic CD8+ T cells, even in the unirradiated tumor, indicative of an abscopal effect. The immune-mediated effects were present regardless of BRAF status. These data suggest that irradiation of brain metastases and anti-PD-1 immunotherapy together can induce abscopal anti-tumor responses that control both local and distant disease.

中文翻译：

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PD-1阻滞与脑转移的联合治疗可在黑色素瘤中诱导有效的抽象作用。

黑色素瘤患者中近一半在疾病过程中发生脑转移。尽管局部放射疗法和全身免疫疗法都取得了进步，但脑转移瘤仍然难以治疗，大多数患者从诊断开始就存活不到5个月。尽管两种治疗方案在治疗转移性黑色素瘤方面均已显示出可观的前景，但人们希望将这些策略结合起来以利用潜在的协同作用。为了研究局部辐射和抗PD-1免疫疗法诱导针对远距离，未辐射肿瘤的有益抗肿瘤免疫反应的能力，我们使用了两种转移性黑色素瘤小鼠模型，分别代表BRAF突变和非突变肿瘤。组合治疗比单独的任何治疗产生更强的全身性抗肿瘤免疫应答。这导致肿瘤的生长减少，甚至在未辐射的肿瘤中，活化的细胞毒性CD8 + T细胞数量也增加，这表明其具有绝对的疗效。无论BRAF状态如何，都存在免疫介导的作用。这些数据表明，脑转移瘤的照射和抗PD-1免疫疗法一起可以诱导控制局部和远处疾病的抽象抗肿瘤反应。