Immune Regulation of the cGAS-STING Signaling Pathway in the Tumor Microenvironment and Its Clinical Application

被引:23
作者
Pu, Feifei [1 ]
Chen, Fengxia [2 ]
Liu, Jianxiang [1 ]
Zhang, Zhicai [1 ]
Shao, Zengwu [1 ]
机构
[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Orthoped, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China
[2] Wuhan Univ, Zhongnan Hosp, Dept Radiat & Med Oncol, Wuhan, Peoples R China
来源
ONCOTARGETS AND THERAPY | 2021年 / 14卷
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
cGAS; STING; innate immunity; tumor; immunotherapy; drug discovery; CYTOSOLIC DNA SENSOR; GMP-AMP SYNTHASE; INDOLEAMINE 2,3-DIOXYGENASE; MITOCHONDRIAL DAMAGE; CANCER-IMMUNOTHERAPY; CYCLIC DINUCLEOTIDES; CELLULAR SENESCENCE; CHECKPOINT BLOCKADE; ANTITUMOR IMMUNITY; ACTIVATION;
D O I
10.2147/OTT.S298958
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
As a DNA receptor in the cytoplasm, cyclic GMP-AMP synthase (cGAS) contributes to the recognition of abnormal DNA in the cytoplasm and contributes to the stimulator of interferon genes (STING) signaling pathway. cGAS could mediate the expression of interferon-related genes, inflammatory-related factors, and downstream chemokines, thus initiating the immune response. The STING protein is a key effector downstream of the DNA receptor pathway. It is widely expressed across cell types such as immune cells,tumor cells, and stromal cells and plays a role in signal transduction for cytoplasmic DNA sensing and immunity. STING agonists, as novel agonists, are used in preclinical research and in the treatment of various tumors via clinical trials and have displayed attractive application prospects. Studying the cGAS-STING signaling pathway will deepen our understanding of tumor immunity and provide a basis for the research and development of antitumor drugs.
引用
收藏
页码:1501 / 1516
页数:16
相关论文
共 171 条
[1]   cGAS in action: Expanding roles in immunity and inflammation [J].
Ablasser, Andrea ;
Chen, Zhijian J. .
SCIENCE, 2019, 363 (6431) :1055-+
[2]   cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING [J].
Ablasser, Andrea ;
Goldeck, Marion ;
Cavlar, Taner ;
Deimling, Tobias ;
Witte, Gregor ;
Roehl, Ingo ;
Hopfner, Karl-Peter ;
Ludwig, Janos ;
Hornung, Veit .
NATURE, 2013, 498 (7454) :380-+
[3]   An overview on Vadimezan (DMXAA): The vascular disrupting agent [J].
Adli, Amir Daei Farshchi ;
Jahanban-Esfahlan, Rana ;
Seidi, Khaled ;
Samandari-Rad, Sonia ;
Zarghami, Nosratollah .
CHEMICAL BIOLOGY & DRUG DESIGN, 2018, 91 (05) :996-1006
[4]   Diverse roles of STING-dependent signaling on the development of cancer [J].
Ahn, J. ;
Konno, H. ;
Barber, G. N. .
ONCOGENE, 2015, 34 (41) :5302-5308
[5]   Self-DNA, STING-dependent signaling and the origins of autoinflammatory disease [J].
Ahn, Jeonghyun ;
Barber, Glen N. .
CURRENT OPINION IN IMMUNOLOGY, 2014, 31 :121-126
[6]   Siple Dome ice reveals two modes of millennial CO2 change during the last ice age [J].
Ahn, Jinho ;
Brook, Edward J. .
NATURE COMMUNICATIONS, 2014, 5
[7]   Cutting Edge: Antimalarial Drugs Inhibit IFN-β Production through Blockade of Cyclic GMP-AMP Synthase-DNA Interaction [J].
An, Jie ;
Woodward, Joshua J. ;
Sasaki, Tomikazu ;
Minie, Mark ;
Elkon, Keith B. .
JOURNAL OF IMMUNOLOGY, 2015, 194 (09) :4089-4093
[8]   Induction of necrotic cell death and activation of STING in the tumor microenvironment via cationic silica nanoparticles leading to enhanced antitumor immunity [J].
An, Myunggi ;
Yu, Chunsong ;
Xi, Jingchao ;
Reyes, Joyce ;
Mao, Guangzhao ;
Wei, Wei-Zen ;
Liu, Haipeng .
NANOSCALE, 2018, 10 (19) :9311-9319
[9]   An Analysis of the Expression and Association with Immune Cell Infiltration of the cGAS/STING Pathway in Pan-Cancer [J].
An, Xiang ;
Zhu, Yuanyuan ;
Zheng, Tongsen ;
Wang, Guangyu ;
Zhang, Minghui ;
Li, Jiade ;
Ji, Hongbo ;
Li, Shijun ;
Yang, Shucai ;
Xu, Dandan ;
Li, Zhiwei ;
Wang, Tianzhen ;
He, Yan ;
Zhang, Lei ;
Yang, Weiwei ;
Zhao, Ran ;
Hao, Dapeng ;
Li, Xiaobo .
MOLECULAR THERAPY-NUCLEIC ACIDS, 2019, 14 :80-89
[10]   cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein-DNA ladders [J].
Andreeva, Liudmila ;
Hiller, Bjoern ;
Kostrewa, Dirk ;
Laessig, Charlotte ;
Mann, Carina C. de Oliveira ;
Drexler, David Jan ;
Maiser, Andreas ;
Gaidt, Moritz ;
Leonhardt, Heinrich ;
Hornung, Veit ;
Hopfner, Karl-Peter .
NATURE, 2017, 549 (7672) :394-+