期刊
IMMUNITY
卷 52, 期 6, 页码 1075-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2020.05.001
关键词
-
类别
资金
- German Research Foundation [SFB1366, 394046768-SFB 1366, SPP 1937 (CE 140/2-2), TRR179 (TP07), SFB-TRR156 (B10N), RTG 2099, 259332240-RTG2099]
- European Commission [H2020-MSCA-MC-ITN-765104-MATURE-NK]
- German Cancer Aid [70112233, 111455]
Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Hypoxia is a common feature of solid tumors, and cells adapt by upregulating the transcription factor HIF-1 alpha. Here, we defined the transcriptional landscape of mouse tumor-infiltrating natural killer (NK) cells by using single-cell RNA sequencing. Conditional deletion of Hif1a in NK cells resulted in reduced tumor growth, elevated expression of activation markers, effector molecules, and an enriched NF-kappa B pathway in tumor-infiltrating NK cells. Interleukin-18 (IL-18) from myeloid cells was required for NF-kappa B activation and the enhanced anti-tumor activity of Hif1a(-/-) NK cells. Extended culture with an HIF-1 alpha inhibitor increased human NK cell responses. Low HIF1A expression was associated with high expression of IFNG in human tumor-infiltrating NK cells, and an enriched NK-IL18-IFNG signature in solid tumors correlated with increased overall patient survival. Thus, inhibition of HIF-1 alpha unleashes NK cell anti-tumor activity and could be exploited for cancer therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据