ArticleJournal for immunotherapy of cancer2021
Intratumoral injection of TLR9 agonist promotes an immunopermissive microenvironment transition and causes cooperative antitumor activity in combination with anti-PD1 in pancreatic cancer.
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 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- An Open-Label Study of Subcutaneous CpG Oligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer.Cancer control : journal of the Moffitt Cancer CenterTrial
- Combinatorial cancer therapy mediated by hydroxyapatite nanoparticles: a comprehensive review.Medical oncology (Northwood, London, England) · 2026Review
- Article
- Multiomics identifies a cholesterol-TFEB-PLD3-TLR9 axis driving immunosuppressive tumor-associated macrophage polarization in esophageal squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Intravenous administration of CpG7909 lipoplex enhances anti-PD1 immunotherapy by modulating the tumor microenvironment and inducing durable tumor regression.Scientific reports · 2025Article
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Lefitolimod in Combination with Ipilimumab in Patients with Advanced Solid Tumors: A Phase I Trial.Journal of immunotherapy and precision oncology · 2025Article
- Review
- Inflammation, microbiota, and pancreatic cancer.Cancer cell international · 2025Review
- Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice.Journal of experimental & clinical cancer research : CR · 2025Article
- Consensus, debate, and prospective on pancreatic cancer treatments.Journal of hematology & oncology · 2024Review
- Targeting Hypoxia-Inducible Factor-1α in Pancreatic Cancer: siRNA Delivery Using Hyaluronic Acid-Displaying Nanoparticles.Pharmaceutics · 2024Article
- Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment.JCO oncology advances · 2024Review
- DAMPs prognostic signature predicts tumor immunotherapy, and identifies immunosuppressive mechanism of pannexin 1 channels in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2024Article
- Cellular collusion: cracking the code of immunosuppression and chemo resistance in PDAC.Frontiers in immunology · 2024Review
- Loss ofFrontiers in immunology · 2024Article
- DNA sensing of dendritic cells in cancer immunotherapy.Frontiers in molecular biosciences · 2024Review
- Injecting hope: the potential of intratumoral immunotherapy for locally advanced and metastatic cancer.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundComplex tumor and immune microenvironment render pancreatic ductal adenocarcinoma (PDAC) resistant to immune checkpoint inhibitors (ICIs). Therefore, a strategy to convert the immune hostile into an immunopermissive tumor is required. Recent studies showed that intratumoral injection of Toll-like receptor 9 agonist IMO-2125 primes the adaptive immune response. Phase I and II trials with intratumoral IMO-2125 demonstrated its safety and antitumoral activity.
methodsWe generated an array of preclinical models by orthotopically engrafting PDAC-derived cell lines in syngeneic mice and categorized them as high, low and no immunogenic potential, based on the ability of tumor to evoke T lymphocyte or NK cell response. To test the antitumor efficacy of IMO-2125 on locally treated and distant sites, we engrafted cancer cells on both flanks of syngeneic mice and treated them with intratumoral IMO-2125 or vehicle, alone or in combination with anti-PD1 ICI. Tumor tissues and systemic immunity were analyzed by transcriptomic, cytofluorimetric and immunohistochemistry analysis.
resultsWe demonstrated that intratumoral IMO-2125 as single agent triggers immune system response to kill local and distant tumors in a selected high immunogenic subtype affecting tumor growth and mice survival. Remarkably, intratumoral IMO-2125 in combination with systemic anti-PD1 causes a potent antitumor effect on primary injected and distant sites also in pancreatic cancer models with low immunogenic potential, preceded by a transition toward an immunopermissive microenvironment, with increase in tumor-infiltrating dendritic and T cells in tumor and lymph nodes.
conclusionWe demonstrated a potent antitumor activity of IMO-2125 and anti-PD1 combination in immunotherapy-resistant PDAC models through the modulation of immune microenvironment, providing the rationale to translate this strategy into a clinical setting.
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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 Socratic graph.