ArticleJournal of experimental & clinical cancer research : CR2024
Tumor-associated neutrophils upregulate Nectin2 expression, creating the immunosuppressive microenvironment in pancreatic ductal adenocarcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global trends in tumor-associated neutrophil research: a bibliometric and visual analysis.Frontiers in immunology · 2025Pooled it
- MIIP Inhibits Colorectal Cancer Progression by Modulating Neutrophils Infiltration and Neutrophil Extracellular Trap Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The deubiquitinase USP5 mediates anti-PD-L1 resistance in breast cancer by stabilizing FOXM1 to upregulate Nectin2.Human cell · 2026Article
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- Beyond EMT: Mesenchymal drift as an emerging driver of stromal-immune reprogramming in prostate cancer.iScience · 2026Review
- Can Complex 3D Models Effectively Replace 2D and Animal Models to Investigate the Microbe-Tumor-Immune Axis in Pancreatic Cancer Studies?Nutrients · 2026Review
- Variable efficacy of the non-covalent KRASNPJ precision oncology · 2026Article
- Vascular SMC-like CAF-derived THBS1 drives tumor-associated neutrophil recruitment to orchestrate an immunosuppressive microenvironment in gastric cancer.Cell death & disease · 2026Article
- Review
- Pan-cancer single-cell atlases of mouse and human tumor-associated dendritic cells.Nature communications · 2026Article
- Targeting tumor-associated macrophages through phytochemicals: a promising strategy for cold tumor therapy.Chinese medicine · 2026Review
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Neutrophil Heterogeneity: Molecules to Cellular Behavior.Life (Basel, Switzerland) · 2026Review
- Noninvasive evaluation and clinical value prediction of tumor-infiltrating neutrophil-to-T-cell ratio in pancreatic ductal adenocarcinoma.NPJ digital medicine · 2026Article
- Neutrophil Plasticity in Airway Disease: Balancing Damage and Repair.Journal of innate immunity · 2026Review
- Rethinking PDAC: from immunological silence to therapeutic opportunity.Frontiers in immunology · 2026Review
- Neutrophil Extracellular Traps in Pancreatic Ductal Adenocarcinoma: A Vicious Cycle in the Tumor Microenvironment and Targeted Interventions.International journal of biological sciences · 2026Review
- Targeting neutrophil-driven immunosuppression: A strategy to overcome immune checkpoint inhibitor resistance.Clinical and translational medicine · 2026Review
- The Ly6gCancer communications (London, England) · 2026Article
- Synergistic Potential of Immune Checkpoint Inhibitor Combined with Neutrophil-Targeted Therapy in Cancer Immunotherapy.Research (Washington, D.C.) · 2026Review
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Authors and funding
19 authors.
Funding
Abstract
backgroundTumor-associated neutrophils (TANs) constitute an abundant component among tumor-infiltrating immune cells and have recently emerged as a critical player in pancreatic ductal adenocarcinoma (PDAC) progression. This study aimed to elucidate the pro-tumor mechanisms of TAN and identify a novel target for effective immunotherapy against PDAC.
methodsMicroarray and cytokine array analyses were performed to identify the mechanisms underlying the function of TANs. Human and mouse TANs were obtained from differentiated HL-60 cells and orthotopically transplanted PDAC tumors, respectively. The interactions of TANs with cancer and cytotoxic T-cells were evaluated through in vitro co-culture and in vivo orthotopic or subcutaneous models. Single-cell transcriptomes from patients with PDAC were analyzed to validate the cellular findings.
resultsIncreased neutrophil infiltration in the tumor microenvironment was associated with poor survival in patients with PDAC. TANs secreted abundant amounts of chemokine ligand 5 (CCL5), subsequently enhancing cancer cell migration and invasion. TANs subpopulations negatively correlated with cytotoxic CD8
conclusionsTANs enhance PDAC progression by secreting CCL5 and upregulating Nectin2. Targeting the immune checkpoint Nectin2 could represent a novel strategy to enhance immunotherapy efficacy in PDAC.
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