气候变化领域集成服务门户(CCPortal): PD-L1 sustains chronic, cancer cell-intrinsic responses to type I interferon, enhancing resistance to DNA damage

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DOI	10.1073/pnas.2112258118
	PD-L1 sustains chronic, cancer cell-intrinsic responses to type I interferon, enhancing resistance to DNA damage
	Cheon H.; Holvey-Bates E.G.; McGrail D.J.; Stark G.R.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:47
英文摘要	Programmed death ligand 1 (PD-L1), an immune-checkpoint protein expressed on cancer cells, also functions independently of the immune system. We found that PD-L1 inhibits the killing of cancer cells in response to DNA damage in an immune-independent manner by suppressing their acute response to type I interferon (IFN; IFN-I). In addition, PD-L1 plays a critical role in sustaining high levels of constitutive expression in cancer cells of a subset of IFNinduced genes, the IFN-related DNA damage resistance signature (IRDS) which, paradoxically, protects cancer cells. The cyclic GMPAMP synthase-stimulator of the IFN genes (cGAS-STING) pathway is constitutively activated in a subset of cancer cells in the presence of high levels of PD-L1, thus leading to a constitutive, low level of IFN-β expression, which in turn increases IRDS expression. The constitutive low level of IFN-β expression is critical for the survival of cancer cells addicted to self-produced IFN-β. Our study reveals immune-independent functions of PD-L1 that inhibit cytotoxic acute responses to IFN-I and promote protective IRDS expression by supporting protective chronic IFN-I responses, both of which enhance the resistance of cancer cells to DNA damage. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CGAS-STING pathway; DNA damage resistance; Programmed death ligand 1 (PD-L1); Type I interferon (IFN-I)
语种	英语
scopus关键词	beta interferon; cyclic GMP AMP synthase; interferon; membrane protein; programmed death 1 ligand 1; stimulator of the IFN gene protein; synthetase; unclassified drug; beta interferon; CD274 protein, human; cGAS protein, human; gamma interferon; interferon; nucleotidyltransferase; programmed death 1 ligand 1; Article; cancer cell; cell survival; controlled study; cytotoxicity; DNA damage; DNA damage response; gene expression; human; human cell; IFN related DNA damage resistance signature; DNA damage; gene expression regulation; genetics; lung tumor; metabolism; physiology; signal transduction; tumor cell line; tumor microenvironment; B7-H1 Antigen; Cell Line, Tumor; DNA Damage; Gene Expression Regulation, Neoplastic; Humans; Interferon Type I; Interferon-beta; Interferon-gamma; Lung Neoplasms; Nucleotidyltransferases; Signal Transduction; Tumor Microenvironment
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250978
作者单位	Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
推荐引用方式 GB/T 7714	Cheon H.,Holvey-Bates E.G.,McGrail D.J.,et al. PD-L1 sustains chronic, cancer cell-intrinsic responses to type I interferon, enhancing resistance to DNA damage[J],2021,118(47).
APA	Cheon H.,Holvey-Bates E.G.,McGrail D.J.,&Stark G.R..(2021).PD-L1 sustains chronic, cancer cell-intrinsic responses to type I interferon, enhancing resistance to DNA damage.Proceedings of the National Academy of Sciences of the United States of America,118(47).
MLA	Cheon H.,et al."PD-L1 sustains chronic, cancer cell-intrinsic responses to type I interferon, enhancing resistance to DNA damage".Proceedings of the National Academy of Sciences of the United States of America 118.47(2021).