免疫监视
NKG2D公司
免疫系统
癌症研究
生物
脑瘤
CD8型
T细胞
缺氧(环境)
细胞毒性T细胞
免疫学
医学
化学
病理
体外
生物化学
有机化学
氧气
作者
Jang Hyun Park,Hyun-Jin Kim,Chae Won Kim,Hyeon Cheol Kim,Yujin Jung,Hyunsoo Lee,Yunah Lee,Young Seok Ju,Ji Eun Oh,Sung‐Hong Park,Jeong Ho Lee,Sung Ki Lee,Heung Kyu Lee
标识
DOI:10.1038/s41590-020-00860-7
摘要
The anatomic location and immunologic characteristics of brain tumors result in strong lymphocyte suppression. Consequently, conventional immunotherapies targeting CD8 T cells are ineffective against brain tumors. Tumor cells escape immunosurveillance by various mechanisms and tumor cell metabolism can affect the metabolic states and functions of tumor-infiltrating lymphocytes. Here, we discovered that brain tumor cells had a particularly high demand for oxygen, which affected γδ T cell-mediated antitumor immune responses but not those of conventional T cells. Specifically, tumor hypoxia activated the γδ T cell protein kinase A pathway at a transcriptional level, resulting in repression of the activatory receptor NKG2D. Alleviating tumor hypoxia reinvigorated NKG2D expression and the antitumor function of γδ T cells. These results reveal a hypoxia-mediated mechanism through which brain tumors and γδ T cells interact and emphasize the importance of γδ T cells for antitumor immunity against brain tumors. Glioblastoma is one of the most intractable tumors and presents a hypoxic and immunologically cold microenvironment. Lee and colleagues demonstrate that normalizing oxygen tension unleashes γδ T cell anti-glioblastoma function.
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