ArticleScientific reports2024
A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The clinical ionizable lipid SM-102 enhances photochemical immunogenic cell death by verteporfin-conjugated liposomes and improves survival in vivo.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- Review
- Quantifying the Dual Effect of Antitumor and Pro-Tumor Human Neutrophils on Natural Killer Cell Behaviors in a Microphysiological System.ACS biomaterials science & engineering · 2026Article
- Neutrophils in glioblastoma: orchestrators of the tumor microenvironment and immune evasion.Molecular biology reports · 2026Review
- Mechano-Organ-on-Chip for Cancer Research.International journal of molecular sciences · 2026Review
- Advances in engineering immune-tumor microenvironments on-a-chip: integrative microfluidic platforms for immunotherapy and drug discovery.Molecular cancer · 2025Review
- Progress in structure-based drug development targeting chemokine receptors.Frontiers in pharmacology · 2025Review
- Construction and application of pancreatic exocrine organoid and spheroid for drug screening and precision medicine.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Cancer cells recruit neutrophils from the bloodstream into the tumor tissue, where these immune cells promote the progression of numerous solid tumors. Studies in mice suggest that blocking neutrophil recruitment to tumors by inhibition of neutrophil chemokine receptor CXCR2 could be a potential immunotherapy for pancreatic cancer. Yet, the mechanisms by which neutrophils promote tumor progression in humans, as well as how CXCR2 inhibition could potentially serve as a cancer therapy, remain elusive. In this study, we developed a human cell-based microphysiological system to quantify neutrophil-tumor spheroid interactions in both "separated" and "contact" scenarios. We found that neutrophils promote the invasion of tumor spheroids through the secretion of soluble factors and direct contact with cancer cells. However, they promote the proliferation of tumor spheroids solely through direct contact. Interestingly, treatment with AZD-5069, a CXCR2 inhibitor, attenuates invasion and proliferation of tumor spheroids by blocking direct contact with neutrophils. Our findings also show that CXCR2 inhibition reduces neutrophil migration toward tumor spheroids. These results shed new light on the tumor-promoting mechanisms of human neutrophils and the tumor-suppressive mechanisms of CXCR2 inhibition in pancreatic cancer and may aid in the design and optimization of novel immunotherapeutic strategies based on neutrophils.
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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.