ArticleCancer immunology research2024
Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer.
Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- Targeting lncRNA-regulated macrophage polarization: a novel therapeutic strategy for pancreatic ductal adenocarcinoma.Journal of physiology and biochemistry · 2026Review
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- CCDC6, a ferroptosis-related gene, modulates stemness features of pancreatic cancer cells in vitro.BMC cancer · 2026Article
- The dual role of the Notch signaling pathway in digestive system cancers.European journal of medical research · 2026Review
- Activated notch signaling pathway protects the intestinal barrier in DSS-induced colitis by regulating tight junctions.European journal of medical research · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Extracellular vesicle-derived miRNA-182-5p educates macrophages towards an immunosuppressive phenotype in pancreatic cancer.Signal transduction and targeted therapy · 2026Article
- Notch-1 induces M2 polarization of tumor-associated macrophages via the YAP/EZH2/FOXD1/CD47 signaling axis, thereby driving non-small cell lung cancer progression.Frontiers in medicine · 2026Article
- Reprogramming the immunosuppressive breast cancer microenvironment: integrating cellular, metabolic, and stromal targets for rational immunotherapy.Frontiers in immunology · 2026Review
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- Pan-cancer analysis of DTX3L as a potential prognostic and immunological biomarker.Scientific reports · 2025Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Advancing the understanding of the role of apoptosis in lung cancer immunotherapy: Global research trends, key themes, and emerging frontiers.Human vaccines & immunotherapeutics · 2025Article
- The complex interplay between diabetes mellitus and pancreatic carcinogenesis: deciphering multifactorial mechanisms and identifying emerging therapeutic vulnerabilities.Cell & bioscience · 2025Review
- Characteristic miRNA profiles represent clinicopathological diversity of small cell lung cancer.The Journal of pathology · 2025Article
- Sciellin inhibits senescence and promotes pancreatic cancer progress by activating the notch signaling pathway.Scientific reports · 2025Article
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16 authors at 1 institution in 1 country.
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Abstract
Pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. The poor survival of patients with PDA has been attributed to a high rate of early metastasis and low efficacy of current therapies, which partly result from its complex immunosuppressive tumor microenvironment. Previous studies from our group and others have shown that tumor-associated macrophages (TAM) are instrumental in maintaining immunosuppression in PDA. Here, we explored the role of Notch signaling, a key regulator of immune response, within the PDA microenvironment. We identified Notch pathway components in multiple immune cell types within human and mouse pancreatic cancer. TAMs, the most abundant immune cell population in the tumor microenvironment, expressed high levels of Notch receptors, with cognate ligands such as JAG1 expressed on tumor epithelial cells, endothelial cells, and fibroblasts. TAMs with activated Notch signaling expressed higher levels of immunosuppressive mediators, suggesting that Notch signaling plays a role in macrophage polarization within the PDA microenvironment. Genetic inhibition of Notch in myeloid cells led to reduced tumor size and decreased macrophage infiltration in an orthotopic PDA model. Combination of pharmacologic Notch inhibition with PD-1 blockade resulted in increased cytotoxic T-cell infiltration, tumor cell apoptosis, and smaller tumor size. Our work implicates macrophage Notch signaling in the establishment of immunosuppression and indicates that targeting the Notch pathway may improve the efficacy of immune-based therapies in patients with PDA.
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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.