ArticleCancer immunology, immunotherapy : CII2018
Cholecystokinin receptor antagonist alters pancreatic cancer microenvironment and increases efficacy of immune checkpoint antibody therapy in mice.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- CCK-1R-selective and non-selective cholecystokinin antagonists, lorglumide, and proglumide increased toxicity of carboplatin to granulocyte-macrophage progenitor cells (CFU-GM) of bone marrow of rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Downregulation of the CCK-B Receptor in Pancreatic Stellate Cells Blocks Molecular Proliferative Pathways and Increases Apoptosis to Decrease Pancreatic Cancer Growth In Vitro.International journal of molecular sciences · 2025Article
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- CCK Receptor Inhibition Reduces Pancreatic Tumor Fibrosis and Promotes Nanoparticle Delivery.Biomedicines · 2024Article
- Article
- Cuproptosis-related lncRNA scoring system to predict the clinical outcome and immune landscape in pancreatic adenocarcinoma.Scientific reports · 2023Article
- Article
- Treatment with a Cholecystokinin Receptor Antagonist, Proglumide, Improves Efficacy of Immune Checkpoint Antibodies in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Tertiary lymphoid structures in pancreatic cancer: a new target for immunotherapy.Frontiers in immunology · 2023Review
- RNA-RNA interactions between SARS-CoV-2 and host benefit viral development and evolution during COVID-19 infection.Briefings in bioinformatics · 2022Article
- Vaccination with Polyclonal Antibody Stimulator (PAS) Prevents Pancreatic Carcinogenesis in the KRAS Mouse Model.Cancer prevention research (Philadelphia, Pa.) · 2021Article
- Dilemma and Challenge of Immunotherapy for Pancreatic Cancer.Digestive diseases and sciences · 2021Review
- Targeting the Cholecystokinin Receptor: A Novel Approach for Treatment and Prevention of Hepatocellular Cancer.Cancer prevention research (Philadelphia, Pa.) · 2021Article
- Pancreatic Cancer and Its Microenvironment-Recent Advances and Current Controversies.International journal of molecular sciences · 2020Review
- A Cholecystokinin Receptor Antagonist Halts Nonalcoholic Steatohepatitis and Prevents Hepatocellular Carcinoma.Digestive diseases and sciences · 2020Article
- Vaccine against gastrin, a polyclonal antibody stimulator, decreases pancreatic cancer metastases.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Gastrin vaccine improves response to immune checkpoint antibody in murine pancreatic cancer by altering the tumor microenvironment.Cancer immunology, immunotherapy : CII · 2019Article
- Genomics meets immunity in pancreatic cancer: Current research and future directions for pancreatic adenocarcinoma immunotherapy.Oncology reviews · 2019Article
- Targeting Multiple Receptors to Increase Checkpoint Blockade Efficacy.International journal of molecular sciences · 2019Review
- Immunotherapy, Radiotherapy, and Hyperthermia: A Combined Therapeutic Approach in Pancreatic Cancer Treatment.Cancers · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells, fibroblasts, and lymphocytes. We hypothesized that CCKR blockade would improve response to immune checkpoint antibodies by promoting influx of tumor-infiltrating lymphocytes (TILs) and reducing fibrosis. We examined the effects of CCKR antagonists or immune checkpoint blockade antibodies alone or in combination in murine models of PDAC. Monotherapy with CCKR blockade significantly decreased tumor size and metastases in SCID mice with orthotopic PDAC, and in C57BL/6 mice, it reduced fibrosis and induced the influx of TILs. Immune-competent mice bearing syngeneic pancreatic cancer (Panc02 and mT3-2D) that were treated with the combination of CCK receptor antagonists and immune checkpoint blockade antibodies survived significantly longer with smaller tumors. Tumor immunohistochemical staining and flow cytometry demonstrated that the tumors of mice treated with the combination regimen had a significant reduction in Foxp3+ T-regulatory cells and an increase in CD4+ and CD8+ lymphocytes. Masson's trichrome stain analysis revealed 50% less fibrosis in the tumors of mice treated with CCKR antagonist compared to controls and compared to checkpoint antibody therapy. CCKR antagonists given with immune checkpoint antibody therapy represent a novel approach for improving survival of PDAC. The mechanism by which this combination therapy improves the survival of PDAC may be related to the decreased fibrosis and immune cells of the tumor microenvironment.
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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.