ArticleCancer immunology research2014
STING ligand c-di-GMP improves cancer vaccination against metastatic breast cancer.
Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.
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Who cites it
134 citing papers in PubMed, 226 citations in OpenAlex.
- Review
- Cyclic di-GMP suppresses cancer metastasis by targeting proteasome 26S subunit non-ATPase 3 independently of STING.Signal transduction and targeted therapy · 2026Article
- Targeting STING elicits GSDMD-dependent pyroptosis and boosts anti-tumor immunity in renal cell carcinoma.Oncogene · 2026Article
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
- The cGAS‒STING pathway in colorectal cancer: bridging innate immunity and therapeutic strategies.Journal of experimental & clinical cancer research : CR · 2025Review
- Emerging Therapeutic Strategies for Lung Cancer: The Role of Immunotherapy and HPV-Targeted Cancer Vaccines.Vaccines · 2025Review
- Recent advances in therapeutic cancer vaccines.Nature reviews. Cancer · 2025Review
- Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment.Molecular cancer · 2025Review
- SARS-CoV-2 N protein exerts antitumor effects in NSCLC by inducing DNA damage and augmenting chemotherapeutic sensitivity.Medical oncology (Northwood, London, England) · 2025Article
- Review
- The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications.Journal of hematology & oncology · 2025Review
- Progress Update on STING Agonists as Vaccine Adjuvants.Vaccines · 2025Review
- Impact and applications of cyclic di-GMP second messenger signaling in biotechnology and medicine.Sustainable microbiology · 2025Review
- Activation of cellular responses by cyclic dinucleotides andJournal of oral microbiology · 2025Article
- Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform 'cold' tumors into 'hot' tumors.Molecular cancer · 2024Review
- cGAS-STING signaling pathway in lung cancer: Regulation on antitumor immunity and application in immunotherapy.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Transcriptome-based characterization of 3'2'-cGAMP signaling mediated immune responses.Computational and structural biotechnology journal · 2024Article
- Non-kinase off-target inhibitory activities of clinically-relevant kinase inhibitors.European journal of medicinal chemistry · 2024Review
- PDE-stable 2'3'-cGAMP analogues, containing 5'-S-phosphorothioester linkage, as STING agonists.RSC medicinal chemistry · 2024Article
- Targeting STING elicits GSDMD-dependent pyroptosis and boosts anti-tumor immunity in renal cell carcinoma.Oncogene · 2024Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Cancer vaccination may be our best and most benign option for preventing or treating metastatic cancer. However, breakthroughs are hampered by immune suppression in the tumor microenvironment. In this study, we analyzed whether cyclic diguanylate (c-di-GMP), a ligand for stimulator of interferon genes (STING), could overcome immune suppression and improve vaccination against metastatic breast cancer. Mice with metastatic breast cancer (4T1 model) were therapeutically immunized with an attenuated Listeria monocytogenes (LM)-based vaccine, expressing tumor-associated antigen Mage-b (LM-Mb), followed by multiple low doses of c-di-GMP (0.2 μmol/L). This treatment resulted in a striking and near elimination of all metastases. Experiments revealed that c-di-GMP targets myeloid-derived suppressor cells (MDSC) and tumor cells. Low doses of c-di-GMP significantly increased the production of IL12 by MDSCs, in correlation with improved T-cell responses to Mage-b, whereas a high dose of c-di-GMP (range, 0.3-3 mmol/L) activated caspase-3 in the 4T1 tumor cells and killed the tumor cells directly. On the basis of these results, we tested one administration of high-dose c-di-GMP (3 mmol/L) followed by repeated administrations of low-dose c-di-GMP (0.2 μmol/L) in the 4T1 model, and found equal efficacy compared with the combination of LM-Mb and c-di-GMP. This finding correlated with a mechanism of improved CD8 T-cell responses to tumor-associated antigens (TAA) Mage-b and Survivin, most likely through cross-presentation of these TAAs from c-di-GMP-killed 4T1 tumor cells, and through c-di-GMP-activated TAA-specific T cells. Our results demonstrate that activation of STING-dependent pathways by c-di-GMP is highly attractive for cancer immunotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.