ArticleNature communications2020
Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- A Randomized Phase II Study of Combination Atezolizumab and Varlilumab (CDX-1127) with or without Cobimetinib in Previously Treated Unresectable Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers.The Journal of clinical investigation · 2021Trial
- Coordinated Immune Activation Following KRAS Inhibition in Syngeneic Models Reveals Molecular Pathways that Potentiate and Limit Antitumor Immunity.Cancer immunology research · 2026Article
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- Dissection of the T cell infiltrate in mouse pancreatic tumors reveals an extensive and diverse tumor-reactive T cell repertoire.Science advances · 2026Article
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- The MEK1/2-IRF4 axis fosters T follicular helper cell differentiationand antitumor humoral immune response.Journal of translational medicine · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Combined targeted and epigenetic-based therapy enhances antitumor immunity by stabilizing GATA6-dependent MHCI expression in pancreatic ductal adenocarcinoma.Nature communications · 2026Article
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Recent advancements in tissue dissociation techniques for cell manufacturing single-cell analysis and downstream processing.Stem cells translational medicine · 2025Review
- Innovative Method for Fully Automated, Enzyme-Free Tissue Dissociation and Preparation for Single-Cell Analysis.Cellular and molecular bioengineering · 2025Article
- Neurofibromatosis Type 1 and MEK Inhibition: A Comprehensive Review with Focus on Selumetinib Therapy.Journal of clinical medicine · 2025Review
- Facts and Hopes of CD40 Agonists in Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Induced clustering of SHP2-depleted tumor cells in vascular islands restores sensitivity to MEK/ERK inhibition.The Journal of clinical investigation · 2025Article
- Article
- Sensitivity of renal cell carcinoma to cuproptosis: a bioinformatics analysis and experimental verification.Journal of Cancer · 2025Article
- CDK4 as a Prognostic Marker of Hepatocellular Carcinoma and CDK4 Inhibitors as Potential Therapeutics.Current medicinal chemistry · 2025Article
- Intermittent MEK Inhibition with GITR Costimulation Rescues T-cell Function for Increased Efficacy with CTLA-4 Blockade in Solid Tumor Models.Cancer immunology research · 2024Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression of immune cell function by cytostatic drugs may limit therapeutic efficacy. Here we show that targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) does not impair dendritic cell-mediated T cell priming and activation. Accordingly, combining MEK inhibitors (MEKi) with agonist antibodies (Abs) targeting the immunostimulatory CD40 receptor results in potent synergistic antitumor efficacy. Detailed analysis of the mechanism of action of MEKi shows that this drug exerts multiple pro-immunogenic effects, including the suppression of M2-type macrophages, myeloid derived suppressor cells and T-regulatory cells. The combination of MEK inhibition with agonist anti-CD40 Ab is therefore a promising therapeutic concept, especially for the treatment of mutant Kras-driven tumors such as pancreatic ductal adenocarcinoma.
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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.