ArticleJournal for immunotherapy of cancer2021
High potency STING agonists engage unique myeloid pathways to reverse pancreatic cancer immune privilege.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 67 citations in OpenAlex.
- An Implantable Scaffold Sequentially Releasing STING Agonist and B7-H3 Antibody for Bone Metastasis Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Tumor microenvironment remodeling by STING agonism sensitizes endothelial cells to cytotoxic anti-PD-L1/L2 antibody.Journal of experimental & clinical cancer research : CR · 2026Article
- IL1R1 blockade augments CD40 agonist mediated immunity in pancreatic cancer.Scientific reports · 2026Article
- A STING signaling relay from tumor cells to macrophages mediates the improved efficacy of combination chemotherapy in pancreatic cancer.Journal of biomedical science · 2026Article
- STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways.Nature communications · 2026Article
- Immune remodeling via mitochondria-dependent STING activation enhances cabozantinib response in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- STING agonism in brain tumours: mechanisms, challenges, and therapeutic advances.Frontiers in oncology · 2026Review
- The cGAS-STING pathway in cancer immunotherapy: prognostic value and therapeutic potential.Frontiers in immunology · 2026Review
- STING-mediated tumor microenvironment remodeling: turning adaptive resistance into therapeutic vulnerability.Frontiers in immunology · 2026Review
- STING signaling pathway: An oasis in the glioblastoma immune desert.Theranostics · 2026Review
- cGAS-STING signaling in the tumor microenvironment induces myeloid cell activation and favors T cell-mediated antitumor immunity.Cancer biology & therapy · 2025Article
- Bridging innate and adaptive tumor immunity: cGAS-STING pathway activation to potentiate immune checkpoint blockade.Journal of experimental & clinical cancer research : CR · 2025Review
- Increased Immunohistochemical Expression of Stimulator of Interferon Genes (STING) in Renal Cancer with Venous Tumor Thrombus Is Associated with Worse Prognosis.Biomedicines · 2025Article
- PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Improvement of the Anticancer Efficacy of PD-1/PD-L1 Blockade: Advances in Molecular Mechanisms and Therapeutic Strategies.MedComm · 2025Review
- Dissecting FAP+ Cell Diversity in Pancreatic Cancer Uncovers an Interferon-Response Subtype of Cancer-Associated Fibroblasts with Tumor-Restraining Properties.Cancer research · 2025Article
- Potentiation of immune checkpoint blockade with an ITPP radiosensitizer studied with oxygen saturation measurements from photoacoustic imaging.Scientific reports · 2025Article
- NLRP3 Inflammasome Activation Expands the Immunosuppressive Myeloid Stroma and Antagonizes the Therapeutic Benefit of STING Activation in Glioblastoma.Cancer research communications · 2025Article
- The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications.Journal of hematology & oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntratumoral injection of cyclic dinucleotide (CDN) agonists of the stimulator of interferon genes (STING) pathway engages innate immune activation and priming of adaptive immune effectors to foster local and distal tumor clearance. Despite proven therapeutic efficacy in preclinical models, a thorough understanding of how CDNs reprogram suppressive myeloid stroma in mouse and man is lacking.
methodsHere, we perform deep transcript-level and protein-level profiling of myeloid-derived suppressor cells and M2 macrophages following stimulation with CDNs of ascending potency. Additionally, we leverage orthotopic
resultsHighly potent synthetic STING agonists repolarize suppressive myeloid populations of human and murine origin in part through inhibition of Myc signaling, metabolic modulation, and antagonism of cell cycle. Surprisingly, high-potency synthetic agonists engage qualitatively unique pathways as compared with natural CDNs. Consistent with our mechanistic observations, we find that intratumoral injection of the highest activity STING agonist, IACS-8803, into orthotopic pancreatic adenocarcinoma lesions unmasks sensitivity to checkpoint blockade immunotherapy. Dimensionality reduction analyses of high parameter flow cytometry data reveals substantial contributions of both myeloid repolarization and T cell activation underlying the in vivo therapeutic benefit of this approach.
conclusionsThis study defines the molecular basis of STING-mediated myeloid reprogramming, revealing previously unappreciated and qualitatively unique pathways engaged by CDNs of ascending potency during functional repolarization. Furthermore, we demonstrate the potential for high potency CDNs to overcome immunotherapy resistance in an orthotopic, multifocal model of PDAC.
Indexed as
Identifiers
What OpenQuestion holds
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.