期刊
CANCER CELL
卷 35, 期 5, 页码 767-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2019.04.003
关键词
-
资金
- Uruguay INNOVA-2
- FMV from ANII
- CABBIO
- PEDECIBA
- ECOS-SUD AUF/FAPESP
- FOCEM (MERCOSUR Structural Convergence Fund) [COF 03/11]
- CSIC UdelaR
- FCE from ANII
- Harry J Lloyd Foundation
- Argentinean Cancer Institute
- Argentinean Agency for Promotion of Science and Technology
- Bunge & Born Foundation
- Sales Foundation
- Richard Lounsbery Foundation
- Wellcome Trust
Although immune checkpoint blockers have yielded significant clinical benefits in patients with different malignancies, the efficacy of these therapies is still limited. Here, we show that disruption of transmembrane protein 176B (TMEM176B) contributes to CD8(+ )T cell-mediated tumor growth inhibition by unleashing inflammasome activation. Lack of Tmem176b enhances the antitumor activity of anti-CTLA-4 antibodies through mechanisms involving caspase-1/IL-1 beta activation. Accordingly, patients responding to checkpoint blockade therapies display an activated inflammasome signature. Finally, we identify BayK8644 as a potent TMEM176B inhibitor that promotes CD8(+)T cell-mediated tumor control and reinforces the antitumor activity of both anti-CTLA-4 and anti-PD-1 antibodies. Thus, pharmacologic de-repression of the inflammasome by targeting TMEM176B may enhance the therapeutic efficacy of immune checkpoint blockers.
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