ArticleCancer research2023
Syk Inhibition Reprograms Tumor-Associated Macrophages and Overcomes Gemcitabine-Induced Immunosuppression in Pancreatic Ductal Adenocarcinoma.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06639724 (A Phase 1b Trial of Perioperative Fostamatinib With Gemcitabine and Nab-paclitaxel in Resectable Pancreatic Cancer), which is not on this map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1b Trial of Perioperative Fostamatinib With Gemcitabine and Nab-paclitaxel in Resectable Pancreatic Cancer
Who cites it
35 citing papers in PubMed, 37 citations in OpenAlex.
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- Tumor slice cultures enable rapid ex vivo profiling of patient-specific drug sensitivity in pancreatic ductal adenocarcinoma.NPJ precision oncology · 2026Article
- Targeting SYK to alleviate MDSC-driven immunosuppression and augment anti-PD1 efficacy.Science China. Life sciences · 2026Article
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- Metabolic Salvage and Acyl-chain Remodeling Support Glycosphingolipid Synthesis within the PDAC Tumor Microenvironment.bioRxiv : the preprint server for biology · 2026Article
- Spatial and phenotypic plasticity of B cells in remodeling the tumor microenvironment.Journal for immunotherapy of cancer · 2026Review
- PHF23-Related Prognostic Signature Modulates Immune Microenvironment and Promotes Tumor Malignancy in Glioma.International journal of molecular sciences · 2026Article
- Hypoxia-driven remodeling of SELENOPNature communications · 2026Article
- Current Advances in Preclinical Patient-Derived Cultivation Models for Individualized Drug Response Prediction in Pancreatic Cancer.Oncology research · 2026Review
- Spatial proteomics of ovarian cancer precursors delineates early disease changes and drug targets.Molecular systems biology · 2026Article
- KRAS-driven cytokine-metabolic crosstalk shapes immune exclusion in pancreatic ductal adenocarcinoma.Frontiers in genetics · 2026Review
- Targeting SYK enhances responses to radiotherapy and PD-1 blockade with myeloid immune remodeling in breast cancer.Frontiers in immunology · 2026Article
- NEK9-mediated Wnt signalling repressor TLE3 rewires Docetaxel resistance in cancer cells by inducing pyroptosis.British journal of cancer · 2025Article
- Beyond the tumor: Enhancing pancreatic cancer therapy through glutamine metabolism and innovative drug delivery.Journal of cell communication and signaling · 2025Review
- Experimental models of pancreas cancer: what has been the impact for precision medicine?The Journal of clinical investigation · 2025Review
- Importance of landscape exploration and progress in molecular therapies and precision medicine for pancreatic ductal adenocarcinoma.World journal of gastrointestinal oncology · 2025Review
- Rational development of gemcitabine-based nanoplatform for targeting SERPINB9/Granzyme B axis to overcome chemo-immune-resistance.Nature communications · 2025Article
- ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer.Molecular cancer · 2025Article
- Orchestration of Tumor-Associated Macrophages in the Tumor Cell-Macrophage-CD8International journal of biological sciences · 2025Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an insidious disease with a low 5-year survival rate. PDAC is characterized by infiltration of abundant tumor-associated macrophages (TAM), which promote immune tolerance and immunotherapeutic resistance. Here we report that macrophage spleen tyrosine kinase (Syk) promotes PDAC growth and metastasis. In orthotopic PDAC mouse models, genetic deletion of myeloid Syk reprogrammed macrophages into immunostimulatory phenotype, increased the infiltration, proliferation, and cytotoxicity of CD8+ T cells, and repressed PDAC growth and metastasis. Furthermore, gemcitabine (Gem) treatment induced an immunosuppressive microenvironment in PDAC by promoting protumorigenic polarization of macrophages. In contrast, treatment with the FDA-approved Syk inhibitor R788 (fostamatinib) remodeled the tumor immune microenvironment, "re-educated" protumorigenic macrophages towards an immunostimulatory phenotype and boosted CD8+ T-cell responses in Gem-treated PDAC in orthotopic mouse models and an ex vivo human pancreatic slice culture model. These findings illustrate the potential of Syk inhibition for enhancing the antitumor immune responses in PDAC and support the clinical evaluation of R788 either alone or together with Gem as a potential treatment strategy for PDAC. SIGNIFICANCE: Syk blockade induces macrophage polarization to an immunostimulatory phenotype, which enhances CD8+ T-cell responses and improves gemcitabine efficacy in pancreatic ductal adenocarcinoma, a clinically challenging malignancy.
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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.