H3-K27M 改变的儿童弥漫性中线神经胶质瘤 (DMG) 是儿童时期出现的侵袭性脑肿瘤。尽管基因组知识取得了进步，并且有大量临床试验测试新的靶向疗法，但患者的治疗结果仍然不足。用适配体等小分子阻断免疫检查点正在开辟新的治疗选择，为这种罕见疾病带来了希望。在此，我们证明 TIM-3 适体作为单一疗法可增加免疫浸润并引发强烈的特异性免疫反应，并有可能提高接受治疗的 DMG 小鼠的总体生存率。重要的是，将 TIM-3 Apt 与放疗相结合可提高总体中位生存期，并在两个儿科 DMG 原位小鼠模型中培养出长期存活的小鼠。有趣的是，与放疗后未治疗组相比，TIM-3适体给药增加了肿瘤微环境中骨髓细胞群的数量和CD8:Tregs的促炎比率。重要的是，T 细胞的消耗导致联合治疗效果的大幅丧失。这项工作揭示了 TIM-3 靶向作为一种免疫治疗方法来改善 DMG 的放疗结果，并为推进使用放疗和 TIM-3 阻断组合治疗这些肿瘤的 I 期临床试验提供了坚实的基础。

Pediatric diffuse midline gliomas (DMG) with H3-K27M-altered are aggressive brain tumors that arise during childhood. Despite advances in genomic knowledge and the significant number of clinical trials testing new targeted therapies, patient outcomes are still insufficient. Immune checkpoint blockades with small molecules, such as aptamers, are opening new therapeutic options that represent hope for this orphan disease. Here, we demonstrated that a TIM-3 aptamer as monotherapy increased the immune infiltration and elicited a strong specific immune response with a tendency to improve the overall survival of treated DMG-bearing mice. Importantly, combining TIM-3 Apt with radiotherapy increased the overall median survival and led to long-term survivor mice in two pediatric DMG orthotopic murine models. Interestingly, TIM-3 aptamer administration increased the number of myeloid populations and the pro-inflammatory ratios of CD8: Tregs in the tumor microenvironment as compared to non-treated groups after radiotherapy. Importantly, the depletion of T-cells led to a major loss of the therapeutic effect achieved by the combination. This work uncovers TIM-3 targeting as an immunotherapy approach to improve the radiotherapy outcome in DMGs and offers a strong foundation for propelling a phase I clinical trial using radiotherapy and TIM-3 blockade combination as a treatment for these tumors.