抗原
薄壁组织
CD8型
生物
树突状细胞
脉络丛
癌症研究
病理
T细胞
抗原提呈细胞
细胞毒性T细胞
脑瘤
中枢神经系统
免疫学
医学
免疫系统
神经科学
生物化学
体外
作者
Jay A. Bowman-Kirigin,Rupen Desai,Brian T. Saunders,Anthony Z. Wang,Maximilian O. Schaettler,Connor J. Liu,Alexandra Livingstone,Dale K. Kobayashi,Vivek Durai,Nicole M. Kretzer,Gregory J. Zipfel,Eric C. Leuthardt,Joshua W. Osbun,Michael R. Chicoine,Albert H. Kim,Theresa L. Murphy,Tanner M. Johanns,Bernd H. Zinselmeyer,Gavin P. Dunn
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2022-11-21
卷期号:11 (1): 20-37
被引量:8
标识
DOI:10.1158/2326-6066.cir-22-0098
摘要
Abstract The central nervous system (CNS) antigen-presenting cell (APC) that primes antitumor CD8+ T-cell responses remains undefined. Elsewhere in the body, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain parenchyma cDC1 are extremely rare; cDCs localize to the choroid plexus and dura. Thus, whether the cDC1 play a function in presenting antigen derived from parenchymal sources in the tumor setting remains unknown. Using preclinical glioblastoma (GBM) models and cDC1-deficient mice, we explored the presently unknown role of cDC1 in CNS antitumor immunity. We determined that, in addition to infiltrating the brain tumor parenchyma itself, cDC1 prime neoantigen-specific CD8+ T cells against brain tumors and mediate checkpoint blockade-induced survival benefit. 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 APC subsets, we identified a tumor-specific fluorescent metabolite of 5-aminolevulinic acid, which fluorescently labeled tumor cells during fluorescence-guided GBM resection. Together, these data elucidate the specialized behavior of cDC1 and suggest that cDC1 play a significant role in CNS antitumor immunity.
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