The central nervous system (CNS) antigen presenting cell (APC) which primes anti-tumor CD8⁺ T cell responses remains undefined. Elsewhere, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain cDC1 are rare; cDC localize to choroid plexus and dura. Using preclinical glioblastoma models and cDC1-deficient mice, we explored the role of cDC1 in CNS anti-tumor immunity. We determined that cDC1 mediate checkpoint blockade-induced survival benefit and prime neoantigen-specific CD8⁺ T cells against brain tumors. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor-antigen. In patient samples, we observed several APC subsets (including the CD141⁺ cDC1-equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same subsets, we identified a tumor-specific fluorescent metabolite of 5- aminolevulinic acid, which labels tumor cells during fluorescence-guided glioblastoma resection. Together, these data elucidate the specialized behavior of cDC1 and suggest cDC1 play a significant role in CNS anti-tumor immunity.

中文翻译：

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传统树突状细胞 1 子集启动 CD8+ T 细胞并运输肿瘤抗原以驱动大脑中的抗肿瘤免疫

引发抗肿瘤 CD8 ⁺ T 细胞反应的中枢神经系统 (CNS) 抗原呈递细胞 (APC)仍未确定。在其他地方，传统的树突状细胞 1 (cDC1) 扮演着这个角色。然而，稳态大脑 cDC1 很少见。cDC 定位于脉络丛和硬脑膜。使用临床前胶质母细胞瘤模型和 cDC1 缺陷小鼠，我们探索了 cDC1 在 CNS 抗肿瘤免疫中的作用。我们确定 cDC1 介导检查点阻断诱导的存活益处，并引发针对脑肿瘤的新抗原特异性 CD8 ⁺ T 细胞。我们观察到 cDC，包括 cDC1，从肿瘤、硬脑膜和 CNS 引流颈部淋巴结中分离出来，含有可追踪的荧光肿瘤抗原。在患者样本中，我们观察到了几个 APC 子集（包括 CD141 ⁺cDC1 等效）浸润性胶质母细胞瘤、脑膜瘤和硬脑膜。在这些相同的亚组中，我们鉴定了 5-氨基乙酰丙酸的肿瘤特异性荧光代谢物，它在荧光引导的胶质母细胞瘤切除术中标记肿瘤细胞。总之，这些数据阐明了 cDC1 的特殊行为，并表明 cDC1 在 CNS 抗肿瘤免疫中发挥着重要作用。