Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenvironments after infusion of virus. We demonstrate that our multiplex biomarker screening platform comprehensively informs changes in both topographical location and functional states of resident/infiltrating immune cells that play a role in neuropathology after treatment with HSV G207 in a pediatric Phase 1 patient. Using this approach, we identified robust infiltration of CD8⁺ T cells suggesting activation of the immune response following virotherapy; however there was a corresponding upregulation of checkpoint proteins PD-1, PD-L1, CTLA-4, and IDO revealing a potential role for checkpoint inhibitors. Such work may ultimately lead to an understanding of the governing pathobiology of tumors, thereby fostering development of novel therapeutics tailored to produce optimal responses.

中文翻译：

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一种新颖的原位多重免疫荧光板，用于评估小儿成胶质细胞瘤中的肿瘤免疫病理学和对病毒疗法的反应，揭示了关卡蛋白抑制作用。

溶瘤性单纯疱疹病毒1疗法的免疫疗法为治疗脑肿瘤提供了一种创新的，靶向的，毒性较小的方法。然而，最大化溶瘤病毒疗法的主要障碍是缺乏对输注病毒后中枢神经系统肿瘤/相关微环境中展现的潜在机制的全面了解。我们证明了我们的多重生物标志物筛选平台全面告知了住院/浸润免疫细胞的地形位置和功能状态的变化，这些细胞在小儿1期患者中用HSV G207治疗后在神经病理学中发挥作用。使用这种方法，我们确定了CD8 ^+的强大浸润T细胞提示病毒治疗后免疫反应的激活；然而，检查点蛋白PD-1，PD-L1，CTLA-4和IDO相应上调，揭示了检查点抑制剂的潜在作用。此类工作可能最终导致对肿瘤的控制病理生物学的理解，从而促进了为产生最佳反应而量身定制的新型疗法的发展。