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

Pu, Feifei; Chen, Fengxia; Liu, Jianxiang; Zhang, Zhicai; Shao, Zengwu

doi:10.2147/ott.s298958

Cited by 13 publications

(5 citation statements)

References 172 publications

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“…However, the cytosolic DNA-sensing pathway is also a double-edged sword and controversial. On one hand, the majority of researchers consider that tumor DNA activates the pathway to induce tumor-antigen presentation and activate the antitumor effector [ 35 , 36 , 37 ]; on the other hand, it releases vast inflammatory mediators to recruit M2 macrophage polarization, which we assume is what happened in our study [ 34 , 38 ].…”

Section: Discussionmentioning

confidence: 68%

Immune-Related LncRNAs to Construct a Prognosis Risk-Assessment Model for Gastric Cancer

et al. 2022

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Background: Gastric cancer is a prevalent cause of tumor death. Tumor immunotherapy aims to reshape the specific immunity to tumors in order to kill the tumor. LncRNAs play a pivotal role in regulating the tumor immune microenvironment. Herein, immune-related lncRNAs were used to establish a prognosis risk-assessment model for gastric cancer and provide personalized predictions while providing insights and targets for gastric cancer treatment to enhance patient prognosis. Methods: Gastric adenocarcinoma transcriptome and clinical data were acquired from the The Cancer Genome Atlas (TCGA) database to screen the immune-related lncRNAs. Then, LASSO COX regression was utilized to construct the prognosis risk-assessment model. Afterward, the reliability of the model was evaluated the relationship between immune infiltration, clinical characteristics, and the model was analyzed. Results: We identified 13 lncRNAs and constructed the prognosis assessment model. According to the median risk score of the training set, the patients were assigned to different risk groups. Overall survival time was shorter in the high-risk group. In the high-risk group, higher infiltration of mono-macrophages, dendritic cells, CD4+ T cells, and CD8+ T cells was observed. Moreover, the model was positively related to tumor metastasis. Conclusion: The prognosis risk-assessment model developed in this research can effectively predict the prognosis of gastric cancer patients. This tool is expected to be further applied to clinics in the future, thus providing a novel target for immunotherapy in gastric cancer patients.

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Section: Discussionmentioning

confidence: 68%

Immune-Related LncRNAs to Construct a Prognosis Risk-Assessment Model for Gastric Cancer

et al. 2022

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“…DMXAA is a STING agonist with anti-tumor activity in mice but fails in clinical trials, as it could not activate human STING. [63][64][65] In contrast, Mn 2+ readily activates the cGAS-STING pathway in cells as it can be actively and efficiently trans-ported into cells. Mn 2+ concentration is ≈ 10 folds in cells than that outside the cells.…”

Section: Discussionmentioning

confidence: 99%

Mn‐Anti‐CTLA4‐CREKA‐Sericin Nanotheragnostics for Enhanced Magnetic Resonance Imaging and Tumor Immunotherapy

Huang,

Wang,

et al. 2023

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The integration of magnetic resonance imaging (MRI), cGAS‐STING, and anti‐CTLA‐4 (aCTLA‐4) based immunotherapy offers new opportunities for tumor precision therapy. However, the precise delivery of aCTLA‐4 and manganese (Mn), an activator of cGAS, to tumors remains a major challenge for enhanced MRI and active immunotherapy. Herein, a theragnostic nanosphere Mn‐CREKA‐aCTLA‐4‐SS (MCCS) is prepared by covalently assembling Mn2+, silk sericin (SS), pentapeptide CREKA, and aCTLA‐4. MCCS are stable with an average size of 160 nm and is almost negatively charged or neutral at pH 5.5/7.4. T1‐weighted images showed MCCS actively targeted tumors to improve the relaxation rate r1 and contrast time of MRI. This studies demonstrated MCCS raises reactive oxygen species levels, activates the cGAS‐STING pathway, stimulates effectors CD8+ and CD80+ T cells, reduces regulatory T cell numbers, and increases IFN‐γ and granzyme secretion, thereby inducing tumor cells autophagy and apoptosis in vitro and in vivo. Also, MCCS are biocompatible and biosafe. These studies show the great potential of Mn‐/SS‐based integrative material MCCS for precision and personalized tumor nanotheragnostics.

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“…Here, we introduce progress in their combination with chemoradiotherapy, immune checkpoint blocking, cancer vaccine, and CAR‐T cells in cancer immunotherapy (Figure 7). 377 …”

Section: Targetting Cgas–sting Signaling Pathway For Disease Therapymentioning

confidence: 99%

cGAS–STING, an important signaling pathway in diseases and their therapy

Li,

Wu,

et al. 2024

MedComm

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Since cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism of cGAS–STING signaling pathway in the past decade. Meanwhile, the triggering and transduction mechanisms have been continuously illuminated. cGAS–STING plays a key role in human diseases, particularly DNA‐triggered inflammatory diseases, making it a potentially effective therapeutic target for inflammation‐related diseases. Here, we aim to summarize the ancient origin of the cGAS–STING defense mechanism, as well as the triggers, transduction, and regulating mechanisms of the cGAS–STING. We will also focus on the important roles of cGAS–STING signal under pathological conditions, such as infections, cancers, autoimmune diseases, neurological diseases, and visceral inflammations, and review the progress in drug development targeting cGAS–STING signaling pathway. The main directions and potential obstacles in the regulating mechanism research and therapeutic drug development of the cGAS–STING signaling pathway for inflammatory diseases and cancers will be discussed. These research advancements expand our understanding of cGAS–STING, provide a theoretical basis for further exploration of the roles of cGAS–STING in diseases, and open up new strategies for targeting cGAS–STING as a promising therapeutic intervention in multiple diseases.

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

Cited by 13 publications

References 172 publications

Immune-Related LncRNAs to Construct a Prognosis Risk-Assessment Model for Gastric Cancer

Immune-Related LncRNAs to Construct a Prognosis Risk-Assessment Model for Gastric Cancer

Mn‐Anti‐CTLA4‐CREKA‐Sericin Nanotheragnostics for Enhanced Magnetic Resonance Imaging and Tumor Immunotherapy

cGAS–STING, an important signaling pathway in diseases and their therapy

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