Review
Immunology
Zhuoying Tian, Yue Zeng, Yurong Peng, Junqi Liu, Fang Wu
Summary: Activation of the cGAS-STING pathway by cytoplasmic DNA leads to the production of Type-1 interferons, which play a critical role in cancer-immunity cycle. Research has shown that combination therapy of STING agonists has made progress in preclinical and clinical trials, but selecting appropriate combination therapy regimens remains a challenge.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Kun Li, Yihang Gong, Dongbo Qiu, Hui Tang, Jian Zhang, Zenan Yuan, Yingqi Huang, Yunfei Qin, Linsen Ye, Yang Yang
Summary: The study found that the chemotherapy agent teniposide effectively activates the cGAS-STING signaling in HCC patients. Combining hyperbaric oxygen therapy can enhance the therapeutic effect of teniposide on HCC and improve the response to PD-1 immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Ziqi Liu, Dan Wang, Jiarong Zhang, Pingjuan Xiang, Zhaoyang Zeng, Wei Xiong, Lei Shi
Summary: The cGAS-STING signaling pathway plays a critical role in regulating the tumor microenvironment by affecting immune activation. It has been widely recognized for its ability to combat tumor progression and induce immune responses, leading to the development of immunotherapies. However, recent findings also suggest its diverse roles in shaping the tumor microenvironment, including functions that promote tumor progression.
Article
Oncology
Si-Yu Wu, Yi Xiao, Jin-Li Wei, Xiao-En Xu, Xi Jin, Xin Hu, Da-Qiang Li, Yi-Zhou Jiang, Zhi-Ming Shao
Summary: This study identified two distinct microenvironment phenotypes, 'inflamed' and 'non-inflamed', within the classic basal-like subtype of TNBC, and revealed that MYC amplification and overexpression led to the formation of the non-inflamed TIME. Combination therapy with a DNA methyltransferase inhibitor and immunotherapy reversed T cell exhaustion and improved T cell function, resulting in potent antitumor activity in MYC-overexpressing TNBC.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
You-Tong Wu, Yan Fang, Qi Wei, Heping Shi, Huiling Tan, Yafang Deng, Zhiqun Zeng, Jian Qiu, Chuo Chen, Lijun Sun, Zhijian J. Chen
Summary: The study demonstrates the development of antibody-drug conjugates (ADCs) by conjugating a STING agonist to tumor-targeting antibodies, which showed well-tolerated systemic administration and potent antitumor efficacy. The STING ADC also promoted multiple aspects of antitumor immune responses, highlighting its potential for clinical development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Liya Ding, Qiwei Wang, Antons Martincuks, Michael J. Kearns, Tao Jiang, Ziying Lin, Xin Cheng, Changli Qian, Shaozhen Xie, Hye-Jung Kim, Inga-Maria Launonen, Anniina Faerkkilae, Thomas M. Roberts, Gordon J. Freeman, Joyce F. Liu, Panagiotis A. Konstantinopoulos, Ursula Matulonis, Hua Yu, Jean J. Zhao
Summary: This study reveals an adaptive immunosuppression mechanism that leads to resistance to PARP inhibition in BRCA1-mutant ovarian tumors. This resistance is mediated by an increased population of protumor tumor-associated macrophages (TAMs) and activation of the STAT3 signaling pathway. The use of STING agonists can reshape the immunosuppressive tumor microenvironment and overcome PARPi resistance in ovarian cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biotechnology & Applied Microbiology
Feifei Pu, Fengxia Chen, Jianxiang Liu, Zhicai Zhang, Zengwu Shao
Summary: cGAS and STING play roles in recognizing abnormal DNA and regulating immune responses in the cytoplasm, with STING agonists showing promising application prospects in tumor treatment.
ONCOTARGETS AND THERAPY
(2021)
Article
Oncology
Casey R. Ager, Akash Boda, Kimal Rajapakshe, Spencer Thomas Lea, Maria Emilia Di Francesco, Priyamvada Jayaprakash, Ravaen B. Slay, Brittany Morrow, Rishika Prasad, Meghan A. Dean, Colm R. Duffy, Cristian Coarfa, Philip Jones, Michael A. Curran
Summary: This study demonstrates that high-potency STING agonists can repolarize suppressive myeloid populations and enhance sensitivity of pancreatic adenocarcinoma to immune checkpoint blockade therapy. The findings provide insights into the unique pathways engaged by CDNs in functional repolarization.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Cunguo Chen, Murong Hu, Yunyun Cao, Binbin Zhu, Jiashe Chen, Yashi Li, Junyi Shao, Sen Zhou, Pengfei Shan, Chen Zheng, Zhongyu Li, Zhiming Li
Summary: In this study, a combined immunotherapy strategy was developed based on immune agonists and photothermal therapy, which can effectively improve the biological efficacy of immunotherapy, transform the immunosuppressive tumor microenvironment into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells.
Article
Multidisciplinary Sciences
Manuel Adrian Suter, Nikki Y. Tan, Chung Hwee Thiam, Muznah Khatoo, Paul A. MacAry, Veronique Angeli, Stephan Gasser, Y. L. Zhang
Summary: Deficiencies in DNA repair and nucleases lead to cytosolic DNA accumulation. The cGAS-STING pathway is important for detecting cytosolic DNA, but its function can be modulated by IL-6 and JAK2/STAT3 signaling pathways in cancer cells, affecting interferon expression and tumor rejection.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Vera M. Kho, Vera E. Mekers, Paul N. Span, Johan Bussink, Gosse J. Adema
Summary: MDSCs are a heterogeneous population of immature immune cells that have suppressive functions in the tumor microenvironment. They play a role in promoting tumor growth by inhibiting the proliferation and function of immune effector cells. The effects of radiotherapy and cGAS/STING signaling on MDSC recruitment, expansion and function are explored in this review, highlighting the key role of cGAS and STING activation in generating systemic anti-tumor immunity after irradiation.
CELLULAR IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Zhian Chen, Zhenhao Li, Huilin Huang, Guodong Shen, Yingxin Ren, Xinyuan Mao, Lingzhi Wang, Zhenyuan Li, Weisheng Wang, Guoxin Li, Bingxia Zhao, Weihong Guo, Yanfeng Hu
Summary: A cancer-cell-membrane biomimetic nanocomposite that enhances the cGAS/STING pathway and suppresses efferocytosis is synthesized. This nanocomposite triggers a combined chemo/chemodynamic therapy when internalized by cancer cells, damaging their nuclear and mitochondrial DNA. It also promotes the burst release of dsDNA fragments, activating the cGAS/STING pathway, enhancing cross-presentation inside dendritic cells, and promoting M1-polarization of tumor-associated macrophages. In vivo experiments demonstrate that this nanocomposite recruits cytotoxic T-cells, facilitates long-term immunological memory, and augments the immune response when combined with immune-checkpoint blockades.
Article
Engineering, Environmental
Wencheng Xu, Luying Qiao, Zhifang Wang, Yanrong Qian, Lei Li, Qianqian Sun, Chunxia Li
Summary: HER2 can inhibit the immune activity of the cGAS-STING pathway, reducing its anti-tumor efficacy. Therefore, by designing a nanosystem and introducing the HER2-specific inhibitor Lapatinib, the immune therapeutic effect of the cGAS-STING pathway can be enhanced.
CHEMICAL ENGINEERING JOURNAL
(2023)
Review
Oncology
Jordan D. Lewicky, Alexandrine L. Martel, Mukul Raj Gupta, Rene Roy, Galaxia M. Rodriguez, Barbara C. Vanderhyden, Hoang-Thanh Le
Summary: Many traditional cancer treatments induce DNA damage, and the cGAS-STING signaling axis helps to explain their immunostimulatory effects. The cGAS-STING axis has the potential to overcome barriers in cancer immunotherapy and address immunosuppressive tumor microenvironments. The balance between antitumor and protumor/inflammatory activities of the cGAS-STING axis is critical in utilizing its immunotherapeutic potential.
Article
Immunology
Joseph R. Podojil, Andrew C. Cogswell, Ming-Yi Chiang, Valerie Eaton, Igal Ifergan, Tobias Neef, Dan Xu, Khyati A. Meghani, Yanni Yu, Sophia M. Orbach, Tushar Murthy, Michael T. Boyne, Adam Elhofy, Lonnie D. Shea, Joshua J. Meeks, Stephen D. Miller
Summary: This study found that the use of ONP-302 can control tumors by reprogramming myeloid cells through the activation of the STING/IL-15/NK cell mechanism, and enhance the efficacy of anti-PD-1.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.