ArticleJournal of hepatology2021
CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 143 citations in OpenAlex.
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- Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma.Cells · 2026Review
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- Advances in Immunotherapy for Intrahepatic Cholangiocarcinoma.International journal of molecular sciences · 2026Review
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.Cancers · 2026Review
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- Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy.Materials today. Bio · 2026Article
- Integrated single-cell and functional analyses define strategies to enhance dendritic cell immunostimulatory capacity.Discover oncology · 2026Article
- Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026Review
- Development of a murine tumor-infiltrating lymphocyte therapy model for cholangiocarcinoma.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Stratifying cholangiocarcinoma: tumor microenvironment, molecular drivers, and novel immunotherapeutic approaches.Clinical and molecular hepatology · 2026Review
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- Oncolytic adenovirus delivery of neoantigens sensitizes low-mutation tumors to anti-PD-1 therapy and prevents metastasis.Signal transduction and targeted therapy · 2025Article
- Genome-annotated bivariate analysis of shared heritability in autoimmune hepatitis with psychiatric comorbidity.Scientific reports · 2025Article
- Research progress on immune checkpoint inhibitors in intrahepatic cholangiocarcinoma.Annals of medicine · 2025Review
- CCL5Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of cisplatin in modulating the tumor immune microenvironment and its combination therapy strategies: a new approach to enhance anti-tumor efficacy.Annals of medicine · 2025Review
- Pharmacological induction of acetyl-CoA carboxylase 1 autophagic degradation attenuates lipid accumulation and cholangiocarcinoma progression.Journal of experimental & clinical cancer research : CR · 2025Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsWhile cholangiocarcinomas (CCAs) commonly express programmed cell death 1 (PD-1) and its ligand (PD-L1), they respond poorly to immune checkpoint inhibitors (ICIs). We aimed to determine whether stimulating antigen-presenting cells, including macrophages and dendritic cells, using a CD40 agonist could improve this response.
methodsWe compared treatment responses in subcutaneous, orthotopic, and 2 plasmid-based murine intrahepatic CCA (iCCA) models. Mice were treated for 4 weeks with weekly IgG control, a CD40 agonistic antibody, anti-PD-1, or the combination of both (anti-CD40/PD-1). Flow cytometric (FACS) analysis of lymphocytes and myeloid cell populations (including activation status) was performed. We used dendritic cell knockout mice, and macrophage, CD4
resultsIn all 4 models, anti-PD-1 alone was minimally efficacious. Mice exhibited a moderate response to CD40 agonist monotherapy. Combination anti-CD40/PD-1 therapy led to a significantly greater reduction in tumor burden. FACS demonstrated increased number and activation of CD4
conclusionCD40-mediated activation of macrophages and dendritic cells in iCCA significantly enhances response to anti-PD-1 therapy. This regimen may enhance the efficacy of first-line chemotherapy. LAY SUMMARY: Checkpoint inhibition, a common form of immune therapy, is generally ineffective for the treatment of cholangiocarcinoma. These tumors suppress the infiltration and function of surrounding immune cells. Stimulating immune cells such as macrophages and dendritic cells via the CD40 receptor activates downstream immune cells and enhances the response to checkpoint inhibitors.
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