ArticleMolecular carcinogenesis2022
The pancreatic cancer immune tumor microenvironment is negatively remodeled by gemcitabine while TGF-β receptor plus dual checkpoint inhibition maintains antitumor immune cells.
Article in Molecular carcinogenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer.medRxiv : the preprint server for health sciences · 2026Article
- Age- and Treatment-Specific TP53 and PI3K Alterations in Pancreatic Ductal Adenocarcinoma (PDAC) Revealed by Conversational Artificial Intelligence.International journal of molecular sciences · 2026Article
- Dual targeting of oncogenic microtubules and mitochondria in PDAC.Oncoscience · 2026Article
- Shuangshen Granule Regulates Tumor Cell Exosomes Through MIF-miR-34a-KLF4 Pathway and Affects Macrophage Polarization Against Lung Cancer.Human mutation · 2026Article
- The value of nucleoporin 188 in diagnosis, prognosis and immunoregulation: from pan-cancer analysis to gastric cancer verification.Frontiers in immunology · 2025Article
- Orchestration of Tumor-Associated Macrophages in the Tumor Cell-Macrophage-CD8International journal of biological sciences · 2025Review
- Cancer-associated fibroblasts: heterogeneity and their role in the tumor immune response.Clinical and experimental medicine · 2024Review
- New avenues for the treatment of immunotherapy-resistant pancreatic cancer.World journal of gastrointestinal oncology · 2024Review
- Decoding tumor-fibrosis interplay: mechanisms, impact on progression, and innovative therapeutic strategies.Frontiers in pharmacology · 2024Review
- A single-cell perspective on immunotherapy for pancreatic cancer: from microenvironment analysis to therapeutic strategy innovation.Frontiers in immunology · 2024Review
- Bromo- and Extra-Terminal Domain Inhibitors Induce Mitochondrial Stress in Pancreatic Ductal Adenocarcinoma.Molecular cancer therapeutics · 2023Article
- Construction and evaluation of a prognostic risk model of tumor metastasis-related genes in patients with non-small cell lung cancer.BMC medical genomics · 2022Article
- Neutrophils in pancreatic cancer: Potential therapeutic targets.Frontiers in oncology · 2022Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDA) tumors have a highly immunosuppressive desmoplastic tumor microenvironment (TME) where immune checkpoint inhibition (ICI) therapy has been exceptionally ineffective. Transforming growth factor-β (TGF-β) receptor activation leads to cancer and immune cell proliferation and phenotype, and cytokine production leading to tumor progression and worse overall survival in PDA patients. We hypothesized that TGF-β receptor inhibition may alter PDA progression and antitumor immunity in the TME. Here, we used a syngeneic preclinical murine model of PDA to explore the impact of TGF-β pathway inhibitor galunisertib (GAL), dual checkpoint immunotherapy (anti-PD-L1 and CTLA-4), the chemotherapy gemcitabine (GEM), and their combinations on antitumor immune responses. Blockade of TGF-β and ICI in immune-competent mice bearing orthotopically injected murine PDA cells significantly inhibited tumor growth and was accompanied by antitumor M1 macrophage infiltration. In contrast, GEM treatment resulted in increased PDA tumor growth, decreased antitumor M1 macrophages, and decreased cytotoxic CD8+ T cell subpopulation compared to control mice. Together, these findings demonstrate the ability of TGF-β inhibition with GAL to prime antitumor immunity in the TME and the curative potential of combining GAL with dual ICI. These preclinical results indicate that targeted inhibition of TGF-β may enhance the efficacy of dual immunotherapy in PDA. Optimal manipulation of the immune TME with non-ICI therapy may enhance therapeutic efficacy.
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