气候变化领域集成服务门户(CCPortal): Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation

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DOI	10.1073/pnas.2025840118
	Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation
	Zhou Y.; Bastian I.N.; Long M.D.; Dow M.; Li W.; Liu T.; Ngu R.K.; Antonucci L.; Huang J.Y.; Phung Q.T.; Zhao X.-H.; Banerjee S.; Lin X.-J.; Wang H.; Dang B.; Choi S.; Karin D.; Su H.; Ellisman M.H.; Jamieson C.; Bosenberg M.; Cheng Z.; Haybaeck J.; Kenner L.; Fisch K.M.; Bourgon R.; Hernandez G.; Lill J.R.; Liu S.; Carter H.; Mellman I.; Karin M.; Shalapour S.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Many cancers evade immune rejection by suppressing major histocompatibility class I (MHC-I) antigen processing and presentation (AgPP). Such cancers do not respond to immune checkpoint inhibitor therapies (ICIT) such as PD-1/PD-L1 [PD-(L)1] blockade. Certain chemotherapeutic drugs augment tumor control by PD-(L)1 inhibitors through potentiation of T-cell priming but whether and how chemotherapy enhances MHC-I–dependent cancer cell recognition by cytotoxic T cells (CTLs) is not entirely clear. We now show that the lysine acetyl transferases p300/CREB binding protein (CBP) control MHC-I AgPPM expression and neoantigen amounts in human cancers. Moreover, we found that two distinct DNA damaging drugs, the platinoid oxaliplatin and the topoisomerase inhibitor mitoxantrone, strongly up-regulate MHC-I AgPP in a manner dependent on activation of nuclear factor kappa B (NF-κB), p300/CBP, and other transcription factors, but independently of autocrine IFNγ signaling. Accordingly, NF-κB and p300 ablations prevent chemotherapy-induced MHC-I AgPP and abrogate rejection of low MHC-I–expressing tumors by reinvigorated CD8+ CTLs. Drugs like oxaliplatin and mitoxantrone may be used to overcome resistance to PD-(L)1 inhibitors in tumors that had “epigenetically down-regulated,” but had not permanently lost MHC-I AgPP activity. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antigen presentation; Histone acetylation; Immune checkpoint inhibitors; MHC-I; NF-κB
语种	英语
scopus关键词	CD8 antigen; cyclic AMP responsive element binding protein binding protein; E1A associated p300 protein; gamma interferon; immunoglobulin enhancer binding protein; major histocompatibility antigen class 1; mitoxantrone; oxaliplatin; antigen presentation; Article; cancer immunotherapy; CD8+ T lymphocyte; controlled study; cytotoxic T lymphocyte; down regulation; gene expression; gene expression regulation; gene induction; human; in vitro study; nonhuman; priority journal; signal transduction; transcription initiation; transcription regulation; tumor immunity; upregulation
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/180582
作者单位	Department of Pharmacology, School of Medicine, University of California, San Diego, CA 92093, United States; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States; Division of Medical Genetics, Health Sciences, Department of Biomedical Informatics, University of California San Diego, San diego, CA 92093, United States; Department of Medicine, University of California San Diego, San diego, CA 92093, United States; Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, San diego, CA 92093, United States; Department of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA 94080, United States; Oncology Department, China Medical University Shengjing Hospital, Shenyang City, 110004, China; Department of Cellular Medicine, Jacqui Wood Cancer Centre, University of Dundee, Dundee, DD1 9SY, United Kingdom; Biomedical Translati...
推荐引用方式 GB/T 7714	Zhou Y.,Bastian I.N.,Long M.D.,et al. Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation[J],2021,118(8).
APA	Zhou Y..,Bastian I.N..,Long M.D..,Dow M..,Li W..,...&Shalapour S..(2021).Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Zhou Y.,et al."Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).