期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-14987-6
关键词
-
资金
- Wilhelm SanderStiftung [2012.056.3]
- Deutsche Krebshilfe [109037, 110662, 110664, 70112332, 70112337]
- Werner Reichenbach Stiftung
- Deutsche Forschungsgemeinschaft [SFB 685, SFB TRR 156/2, RO 764/14-1, RO 764/15-1, SFB 773, Wi 1279/4-1]
- Cluster of Excellence iFIT Image-Guided and Functionally Instructed Tumor Therapies, University of Tubingen, Germany - Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy [EXC 2180, EXC 2180 - 390900677]
Immune checkpoint blockade (ICB)-based or natural cancer immune responses largely eliminate tumours. Yet, they require additional mechanisms to arrest those cancer cells that are not rejected. Cytokine-induced senescence (CIS) can stably arrest cancer cells, suggesting that interferon-dependent induction of senescence-inducing cell cycle regulators is needed to control those cancer cells that escape from killing. Here we report in two different cancers sensitive to T cell-mediated rejection, that deletion of the senescence-inducing cell cycle regulators p16(Ink4a)/p19(Arf) (Cdkn2a) or p21(Cip1) (Cdkn1a) in the tumour cells abrogates both the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB have losses of senescence-inducing genes and amplifications of senescence inhibitors. Metastatic cells also resist CIS. Such genetic and functional alterations are infrequent in metastatic melanomas regressing during ICB. Thus, activation of tumour-intrinsic, senescence-inducing cell cycle regulators is required to stably arrest cancer cells that escape from eradication.
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