ArticleTranslational oncology2020
Gemcitabine Recruits M2-Type Tumor-Associated Macrophages into the Stroma of Pancreatic Cancer.
Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- The immune microenvironment and relation to outcome in patients with advanced breast cancer treated with docetaxel with or without gemcitabine.Oncoimmunology · 2021Trial
- Research advances on tumor-associated macrophages in pancreatic cancer.Biochemistry and biophysics reports · 2026Review
- Chemotherapeutics as Immune Modulators for the Treatment of Triple-Negative Breast Cancer.Cancers · 2026Review
- Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions.Signal transduction and targeted therapy · 2026Review
- Targeting Prolyl 3-hydroxylase 1 inhibits pancreatic cancer progression and macrophage immunity.Nature communications · 2026Article
- Article
- Gemcitabine: immunomodulatory or immunosuppressive role in the tumor microenvironment.Frontiers in immunology · 2025Review
- New insights into SYK targeting in solid tumors.Trends in pharmacological sciences · 2024Review
- Multicellular tumor spheroid model to study the multifaceted role of tumor-associated macrophages in PDAC.Drug delivery and translational research · 2024Article
- Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.Medical oncology (Northwood, London, England) · 2024Review
- Near-infrared Absorption and Emission Probes with Optimal Connection Bridges for Live Monitoring of NAD(P)H Dynamics in Living Systems.Sensors and actuators. B, Chemical · 2024Article
- Targeting circulating tumor cells to prevent metastases.Human cell · 2024Review
- Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment.JCO oncology advances · 2024Review
- Statins abrogate gemcitabine-induced PD-L1 expression in pancreatic cancer-associated fibroblasts and cancer cells with improved therapeutic outcome.Cancer immunology, immunotherapy : CII · 2023Article
- Syk Inhibition Reprograms Tumor-Associated Macrophages and Overcomes Gemcitabine-Induced Immunosuppression in Pancreatic Ductal Adenocarcinoma.Cancer research · 2023Article
- Polarization of Cancer-Associated Macrophages Maneuver Neoplastic Attributes of Pancreatic Ductal Adenocarcinoma.Cancers · 2023Review
- Human pancreatic cancer patients with Epithelial-to-Mesenchymal Transition and an aggressive phenotype show a disturbed balance in Protein Phosphatase Type 2A expression and functionality.Journal of translational medicine · 2023Article
- Single-cell RNA sequencing revealed subclonal heterogeneity and gene signatures of gemcitabine sensitivity in pancreatic cancer.Frontiers in pharmacology · 2023Article
- Immunotherapy-based novel nanoparticles in the treatment of gastrointestinal cancer: Trends and challenges.World journal of gastroenterology · 2022Review
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is a very lethal disease that can develop therapy resistance over time. The dense stroma in PDAC plays a critical role in tumor progression and resistance. How this stroma interacts with the tumor cells and how this is influenced by chemotherapy remain poorly understood.
methodsThe backbone of this study is the parallel transcriptome analysis of human tumor and mouse stroma in two molecular and clinical representative patient-derived tumor xenografts models. Mice (8 animals per group) were treated for 4 weeks with gemcitabine or control. We studied tumor growth, RNA expression in the stroma, tumor-associated macrophages (TAMs) with immunofluorescence, and cytokines in the serum.
resultsA method for parallel transcriptome analysis was optimized. We found that the tumor (differentiation, gene expression) determines the infiltration of macrophages into the stroma. In aggressive PDAC (epithelial-to-mesenchymal transition high), we find more M2 polarized TAMs and the activation of cytokines and growth factors (TNFα, TGFβ1, and IL6). There are increased stromal glycolysis, reduced fatty acid oxidation, and reduced mitochondrial oxidation (tricarboxylic acid cycle and oxidative phosphorylation). Treatment with gemcitabine results in a shift of innate immune cells, especially additional infiltration of protumoral M2 TAMs (P < .001) and metabolic reprogramming.
conclusionsGemcitabine treatment of PDAC xenografts stimulates a protumoral macrophage phenotype, and this, in combination with a shift of the tumor cells to a mesenchymal phenotype that we reported previously, contributes to tumor progression and therapeutic resistance. Targeting M2-polarized TAMs may benefit PDAC patients at risk to become refractory to current anticancer regimens.
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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.