ArticleThe Journal of experimental medicine2023
WNT signaling in the tumor microenvironment promotes immunosuppression in murine pancreatic cancer.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer.Cancer discovery · 2026Article
- CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis.Nature communications · 2026Article
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Hypoxia-Induced Fibroblast IL-6 Promotes Immunosuppressive Macrophage Phenotypes in Pancreatic Cancer.Cells · 2026Article
- A stromal PAI1-tPA axis orchestrates immunosuppression in pancreatic cancer.Science advances · 2026Article
- Wilms Tumor 1-Expressing Stromal Cells Promote Pancreatic Cancer Progression.Cancer research · 2026Article
- Prognostic and Immunological Value of CTNNB1 in Pancreatic Adenocarcinoma: A Comprehensive NGS and Multicomponent Analysis.Genetics research · 2026Article
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- Clinical and Fundamental Research Progressions on Tumor-Infiltrating Lymphocytes Therapy in Cancer.Vaccines · 2025Review
- Deciphering the heterogeneity of epithelial cells in pancreatic ductal adenocarcinoma: implications for metastasis and immune evasion.World journal of surgical oncology · 2025Article
- A novel peptide RR-171 derived from human umbilical cord serum induces apoptosis and pyroptosis in pancreatic cancer cells.Scientific reports · 2025Article
- Signature Construction Associated with Tumor-Infiltrating Macrophages Identifies IRF8 as a Novel Biomarker for Immunotherapy in Advanced Gastric Cancer.International journal of molecular sciences · 2025Article
- Review
- JPI-547, a Dual Inhibitor of PARP/Tankyrase, Shows Antitumor Activity Against Pancreatic Cancers with Homologous Recombination Repair Deficiency or Wnt-Addiction.International journal of biological sciences · 2025Article
- Role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer (Review).Oncology reports · 2024Review
- Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth.Cancer discovery · 2024Article
- Article
- Pancreatic Epithelial IL17/IL17RA Signaling Drives B7-H4 Expression to Promote Tumorigenesis.Cancer immunology research · 2024Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDA) is associated with activation of WNT signaling. Whether this signaling pathway regulates the tumor microenvironment has remained unexplored. Through single-cell RNA sequencing of human pancreatic cancer, we discovered that tumor-infiltrating CD4+ T cells express TCF7, encoding for the transcription factor TCF1. We conditionally inactivated Tcf7 in CD4 expressing T cells in a mouse model of pancreatic cancer and observed changes in the tumor immune microenvironment, including more CD8+ T cells and fewer regulatory T cells, but also compensatory upregulation of PD-L1. We then used a clinically available inhibitor of Porcupine, a key component of WNT signaling, and observed similar reprogramming of the immune response. WNT signaling inhibition has limited therapeutic window due to toxicity, and PD-L1 blockade has been ineffective in PDA. Here, we show that combination targeting reduces pancreatic cancer growth in an experimental model and might benefit the treatment of pancreatic cancer.
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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.