ArticleGut2022
Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis.
Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The trial behind it
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Who cites it
68 citing papers in PubMed, 104 citations in OpenAlex.
- Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Blockage of cuproplasia inhibits pancreatic tumour-associated neutrophils infiltration through TRAF6/STAT3/CCL2 pathway.British journal of cancer · 2026Article
- Extracellular vesicles from chemotherapy-induced senescent tumor cells reprogram hepatic phospholipid metabolism to promote pancreatic cancer liver metastasis.Journal of experimental & clinical cancer research : CR · 2026Article
- Pancreatic cancer.Nature reviews. Disease primers · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- The IGF2BP3/SLC2A1 axis mediates hsa_circ_0000376-Induced malignant progression and neutrophil N2 polarization in the lung adenocarcinoma microenvironment.Journal of molecular histology · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Tumor-associated neutrophils in pancreatic ductal adenocarcinoma: mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Neutrophils and neutrophil extracellular traps: double-edged swords in cancer pathophysiology and therapy resistance.Cell communication and signaling : CCS · 2025Review
- Calumenin, A Calcium-Binding Modulatory Protein, Effective in Pathological Calcifications and Cancers, With Therapeutic Application Promise.FASEB bioAdvances · 2025Review
- Single-cell transcriptome analysis identifies MIF as a novel tumor-associated neutrophil marker for pancreatic ductal adenocarcinoma.NPJ precision oncology · 2025Article
- Integrated spatial omics of metabolic reprogramming and the tumor microenvironment in pancreatic cancer.iScience · 2025Article
- Improving outcomes of patients with pancreatic cancer.Nature reviews. Clinical oncology · 2025Review
- Four genes shared between rheumatoid arthritis and cervical cancer are associated with cervical cancer prognosis.Scientific reports · 2025Article
- AXL-Mediated Drug Resistance in ALK-Rearranged NSCLC Enhanced by GAS6 From Macrophages and MMP11 Positive Fibroblasts.Cancer science · 2025Article
- Tumor‑associated neutrophils: Critical regulators in cancer progression and therapeutic resistance (Review).International journal of oncology · 2025Review
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease and cytotoxic chemotherapy is the standard of care treatment for patients with advanced disease. Here, we investigate how the microenvironment in PDAC liver metastases reacts to chemotherapy and its role in metastatic disease progression post-treatment, an area which is poorly understood.
designThe impact of chemotherapy on metastatic disease progression and immune cell infiltrates was characterised using flow and mass cytometry combined with transcriptional and histopathological analysis in experimental PDAC liver metastases mouse models. Findings were validated in patient derived liver metastases and in an autochthonous PDAC mouse model. Human and murine primary cell cocultures and ex vivo patient-derived liver explants were deployed to gain mechanistical insights on whether and how chemotherapy affects the metastatic tumour microenvironment.
resultsWe show that in vivo, chemotherapy induces an initial infiltration of proinflammatory macrophages into the liver and activates cytotoxic T cells, leading only to a temporary restraining of metastatic disease progression. However, after stopping treatment, neutrophils are recruited to the metastatic liver via CXCL1 and 2 secretion by metastatic tumour cells. These neutrophils express growth arrest specific 6 (Gas6) which leads to AXL receptor activation on tumour cells enabling their regrowth. Disruption of neutrophil infiltration or inhibition of the Gas6/AXL signalling axis in combination with chemotherapy inhibits metastatic growth. Chemotherapy increases Gas6 expression in circulating neutrophils from patients with metastatic pancreatic cancer and recombinant Gas6 is sufficient to promote tumour cell proliferation ex vivo, in patient-derived metastatic liver explants.
conclusionCombining chemotherapy with Gas6/AXL or neutrophil targeted therapy could provide a therapeutic benefit for patients with metastatic pancreatic cancer.
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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.