Article
Cell Biology
Aida S. S. Hansen, Lea S. S. Jensen, Kristine R. R. Gammelgaard, Kristoffer G. G. Ryttersgaard, Christian Krapp, Jesper Just, Kasper L. L. Jonsson, Pia B. B. Jensen, Thomas Boesen, Mogens Johansen, Anders Etzerodt, Bent W. W. Deleuran, Martin R. R. Jakobsen
Summary: This article introduces the highly immunosuppressive tumor microenvironment, and explores a novel method to improve immunotherapy effectiveness by activating the STING signaling pathway. The researchers found that extracellular vesicles derived from activated CD4(+) T cells can sensitize macrophages and activate the STING pathway, effectively disrupting the immune suppressive environment in the tumor and priming for a robust immune response towards STING activation.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Chemistry, Multidisciplinary
Samuele Stazzoni, Daniel F. R. Bohmer, Fabian Hernichel, Dilara Oezdemir, Aikaterini Pappa, David Drexler, Stefan Bauernfried, Gregor Witte, Mirko Wagner, Simon Veth, Karl-Peter Hopfner, Veit Hornung, Lars M. Koenig, Thomas Carell
Summary: 2',3'-cGAMP is a second messenger formed during cellular recognition of foreign cytosolic DNA, binding to the adaptor protein STING to induce an immune response. Studies show that analogs lacking secondary ribose-OH groups can serve as poxin-resistant STING agonists, with dideoxy-2',3'-cAAMP showing high antitumor response in mice.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Steven E. Caldwell, Chasity P. Janosko, Alexander Deiters
Summary: In this study, a light-activated STING agonist was developed to selectively activate the STING pathway by blocking a key interaction. This finding expands the toolbox of conditionally controlled STING agonists and provides a potential solution to avoid systemic immune activation.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Immunology
Nanxin Liu, Xiaoxiao Pang, Hua Zhang, Ping Ji
Summary: The cGAS-STING pathway is crucial in protecting the host against viral infections and has also been found to play a role in response to bacterial infections. However, its functions in bacterial infections are more complex and diverse compared to viral infections, as the effects on the host vary depending on the bacterial species and infection mode.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Bakhos Jneid, Aurore Bochnakian, Caroline Hoffmann, Fabien Delisle, Emeline Djacoto, Philemon Sirven, Jordan Denizeau, Christine Sedlik, Yohan Gerber-Ferder, Frederic Fiore, Ramazan Akyol, Carine Brousse, Robert Kramer, Ian Walters, Sylvain Carlioz, Helene Salmon, Bernard Malissen, Marc Dalod, Eliane Piaggio, Nicolas Manel
Summary: Activation of STING in immunogenic tumors can induce antitumor T cell response, but it remains unclear how to apply it in nonimmunogenic tumors. This study showed that intratumoral delivery of cGAMP-VLP activated T cells and reduced tumor regulatory T cells, synergizing with PD1 blockade. However, intratumoral administration of the synthetic CDN ADU-S100 caused tumor necrosis and systemic T cell activation, but depleted immune cells and minimally primed circulating tumor-specific T cells. Thus, cell targeting of STING stimulation shapes the antitumor T cell response and provides a strategy to enhance T cell-targeted immunotherapy.
SCIENCE IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
M. Petrovic, G. Borchard, O. Jordan
Summary: Studies have shown the significance of the cGAS-STING pathway in anticancer immunity, but issues exist with cGAMP as a ligand, such as susceptibility to degradation and difficulty in transfecting into negatively charged membrane cells. Therefore, a suitable carrier is needed to enhance transfection efficiency and protect cGAMP.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Multidisciplinary
Lei Wang, Han Zhou, Qingjing Chen, Zhiwen Lin, Chenwei Jiang, Xingte Chen, Mingdong Chen, Libin Liu, Lingdong Shao, Xiaolong Liu, Jianji Pan, Jingcheng Wu, Jibin Song, Junxin Wu, Da Zhang
Summary: This study highlights the importance of incorporating catalytic radiosensitizers and STING agonists into radioimmunotherapy for rectal cancer (RC). The combination of DMPtNPS and radiotherapy (RT) has the potential to decrease tumor hypoxia and enhance radiosensitivity, while provoking bidirectional regulatory effects on the immune response. Loading cGAMP on DMPtNPS can reverse the negative impact on the immune response and improve immunotherapy through the type I interferon pathway.
Review
Oncology
Quanjin Li, Pu Gao
Summary: Biomolecular condensates formed by phase separation play critical roles in cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. The regulation and activation mechanisms of these condensates are under investigation, offering new opportunities for drug discovery.
FRONTIERS OF MEDICINE
(2023)
Article
Multidisciplinary Sciences
Jacqueline A. Carozza, Anthony F. Cordova, Jenifer A. Brown, Yasmeen AlSaif, Volker Bohnert, Xujun Cao, Rachel E. Mardjuki, Gemini Skariah, Daniel Fernandez, Lingyin Li
Summary: This study found that extracellular cGAMP acts as a pivotal STING activator in antiviral immunity and systemic inflammation. It also identified an evolutionarily critical role for ENPP1 in regulating inflammation and suggested a therapeutic strategy for viral and inflammatory conditions by manipulating ENPP1 activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Natasha Samson, Andrea Ablasser
Summary: The cGAS-STING pathway plays a critical role in cancer and can affect tumor development and treatment outcomes. This article discusses the impact of cGAS-STING signaling on tumors and highlights current research efforts in this field.
Review
Biotechnology & Applied Microbiology
Tabea Bartsch, Martin Becker, Jascha Rolf, Katrin Rosenthal, Stephan Lutz
Summary: Cyclic dinucleotides (CDNs), as strong agonists of the stimulator of interferon genes, have great potential in pharmaceutical applications. The synthesis of CDNs through chemical and biocatalytic methods has its advantages and challenges. This review discusses the latest discoveries and trends in CDN synthesis, with a focus on the most promising biotechnological processes for CDN production.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Fisheries
Xue Qiao, Youjing Li, Yuhao Jin, Sicong Wang, Lilin Hou, Lingling Wang, Linsheng Song
Summary: In this study, a member of interferon-stimulated genes, IFI44L, was identified in Pacific oysters. The expression of IFI44L was found to be highest in haemocytes, and its expression was regulated by CgIFNLP and CgSTAT. IFI44L was involved in the antiviral immune response in oysters.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Claire Coderch, Javier Arranz-Herrero, Estanislao Nistal-Villan, Beatriz de Pascual-Teresa, Sergio Rius-Rocabert
Summary: STING is an adaptor protein involved in immune response activation in vertebrates. Its induction can trigger early immune response and be used in cancer immune treatments. Understanding the activation of STING is crucial in designing therapeutic drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Zhuohao Ruan, Genghua Chen, Tingting Xie, Guodong Mo, Guiyan Wang, Wen Luo, Hongmei Li, Meiqing Shi, Wen-sheng Liu, Xiquan Zhang
Summary: The study demonstrates that chicken CIS protein promotes ALV-J replication by inhibiting the expression of interferon and interferon-stimulated genes, while its silencing helps to resist the ALV-J virus.
Article
Multidisciplinary Sciences
John A. McIntosh, Zhijian Liu, Brian M. Andresen, Nastaran Salehi Marzijarani, Jeffrey C. Moore, Nicholas M. Marshall, Margie Borra-Garske, Jennifer Obligacion, Patrick S. Fier, Feng Peng, Jacob H. Forstater, Matthew S. Winston, Chihui An, Wonsuk Chang, Jongwon Lim, Mark A. Huffman, Steven P. Miller, Fuh-Rong Tsay, Michael D. Altman, Charles A. Lesburg, Dietrich Steinhuebel, B. Wesley Trotter, Jared N. Cumming, Alan Northrup, Xiaodong Bu, Benjamin F. Mann, Mirlinda Biba, Kaori Hiraga, Grant S. Murphy, Joshua N. Kolev, Amanda Makarewicz, Weilan Pan, Iman Farasat, Rachel S. Bade, Kevin Stone, Da Duan, Oscar Alvizo, Donovan Adpressa, Erik Guetschow, Erik Hoyt, Erik L. Regalado, Steve Castro, Nelo Rivera, Joseph P. Smith, Fengqiang Wang, Alejandro Crespo, Deeptak Verma, Stephanus Axnanda, Zachary E. X. Dance, Paul N. Devine, David Tschaen, Keith A. Canada, Paul G. Bulger, Benjamin D. Sherry, Matthew D. Truppo, Rebecca T. Ruck, Louis-Charles Campeau, David Jonathan Bennett, Guy R. Humphrey, Kevin R. Campos, Matthew L. Maddess
Summary: Introducing molecular complexity in a efficient manner is a challenging goal in modern synthetic chemistry. Artificial biosynthetic pathways utilizing enzymes have the ability to carry out multiple synthetic steps simultaneously, enabling the discovery and production of complex, non-natural molecules. In this study, an enzymatic cascade was discovered and constructed for the synthesis of MK-1454, a potential immuno-oncology therapeutic. By engineering the enzymes involved, multiple steps of the synthesis were successfully carried out in a one-pot reaction.
