ArticleJournal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract2022
TGF-β Alters the Proportion of Infiltrating Immune Cells in a Pancreatic Ductal Adenocarcinoma.
Article in Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- Platelets as localized conduits of TGF-β1 in the tumor microenvironment: implications for cancer progression and therapy.Human cell · 2026Review
- Liver X receptor: A potential target for inflammatory bowel disease and colorectal cancer (Review).Molecular medicine reports · 2026Review
- Reprogramming dendritic cells to overcome tumor-mediated immune suppression.Frontiers in immunology · 2026Review
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Mathematical strategies for predicting resistant subpopulations from scRNAseq data of a PANC-1 3D tissue model: Insight into gemcitabine resistance and TGFB1-induced invasion and EMT.Computational and structural biotechnology journal · 2025Article
- TGFB2 mRNA Levels Prognostically Interact with Interferon-Alpha Receptor Activation of IRF9 and IFI27, and an Immune Checkpoint LGALS9 to Impact Overall Survival in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2024Article
- Long non-coding RNA PVT1 regulates TGF-β and promotes the proliferation, migration and invasion of hypopharyngeal carcinoma FaDu cells.World journal of surgical oncology · 2024Article
- ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8Nature communications · 2024Article
- Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy.Journal of hematology & oncology · 2024Review
- Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- Congenital disorders of glycosylation with multiorgan disruption and immune dysregulation caused by compound heterozygous variants in MAN2B2.Molecular genetics & genomic medicine · 2024Article
- Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment.JCO oncology advances · 2024Review
- Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse.Frontiers in immunology · 2023Article
- Using Single Cell Transcriptomics to Elucidate the Myeloid Compartment in Pancreatic Cancer.Frontiers in oncology · 2022Review
- Article
- TGFβ Signaling in the Pancreatic Tumor Microenvironment.Cancers · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeImmunotherapy, such as checkpoint inhibitors against anti-programmed death-ligand 1 (PD-L1), has not been successful in treating patients with pancreatic ductal adenocarcinoma (PDAC). Tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), and the TGF-β cytokine are critical in anti-cancer immunity. We hypothesized that TGF-β enhances the immunosuppressive effects of TAM, MDSC, and DC presence in tumors.
methodsUsing a murine PDAC cell line derived from a genetically engineered mouse model, we orthotopically implanted treated cells plus drug embedded in Matrigel into immunocompetent mice. Treatments included saline control, TGF-β1, or a TGF-β receptor 1 small molecule inhibitor, galunisertib. We investigated TAM, MDSC, DC, and TAM PD-L1 expression with flow cytometry in tumors. Separately, we used the TIMER2.0 database to analyze TAM and PD-L1 gene expression in human PDAC tumors in TCGA database.
resultsTGF-β did not alter MDSC or DC frequencies in the primary tumors. However, in PDAC metastases to the liver, TGF-β decreased the proportion of MDSCs (P=0.022) and DCs (P=0.005). TGF-β significantly increased the percent of high PD-L1 expressing TAMs (32 ± 6 % vs. 12 ± 5%, P=0.013) but not the proportion of TAMs in primary and metastatic tumors. TAM PD-L1 gene expression in TCGA PDAC database was significantly correlated with tgb1 and tgfbr1 gene expression (P<0.01).
conclusionsTGF-β is important in PDAC anti-tumor immunity, demonstrating context-dependent impact on immune cells. TGF-β has an overall immunosuppressive effect mediated by TAM PD-L1 expression and decreased presence of DCs. Future investigations will focus on enhancing anti-cancer immune effects of TGF-β receptor inhibition.
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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.