Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cured most mice in two glioma models. This treatment was associated with macrophage influx and M1-like polarization, along with increased T effector to T regulatory cell ratios. Immune cell depletion studies demonstrated that CD4⁺ and CD8⁺ T cells as well as macrophages are required for synergistic curative activity. This combination should be translatable to the clinic and other immunosuppressive cancers.

中文翻译：

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巨噬细胞极化通过免疫免疫疗法和免疫检查站封锁相结合，有助于根除胶质母细胞瘤。

胶质母细胞瘤是一种免疫抑制性致命性脑癌，其中包含胶质母细胞瘤干样细胞（GSC）。溶瘤性单纯疱疹病毒（oHSV）在癌细胞中选择性复制，同时诱导抗肿瘤免疫力。表达oHSVG47Δ的小鼠IL-12（G47Δ-mIL12），免疫检查点抗体（CTLA-4，PD-1，PD-L1）或双重组合适度延长了小鼠神经胶质瘤模型的生存期。但是，在两个神经胶质瘤模型中，抗CTLA-4，抗PD-1和G47Δ-mIL12的三联组合治愈了大多数小鼠。这种治疗与巨噬细胞的涌入和M1样极化有关，并伴随着T效应子与T调节细胞的比率增加。免疫细胞耗竭研究表明CD4 ⁺和CD8 ⁺T细胞和巨噬细胞是协同治疗的必要条件。这种组合应可转化为临床和其他免疫抑制性癌症。