ArticleOncotarget2016
Gemcitabine inhibits immune escape of pancreatic cancer by down regulating the soluble ULBP2 protein.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses.PloS one · 2023Pooled it
- High-throughput proteomics of breast cancer interstitial fluid: identification of tumor subtype-specific serologically relevant biomarkers.Molecular oncology · 2021Trial
- Integrated multi-omics analysis of UL16-binding protein 2 as a prognostic and immunotherapy biomarker for colorectal cancer.Functional & integrative genomics · 2025Article
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- Review
- Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer.Scientific reports · 2023Article
- Ovarian cancer treatment and natural killer cell-based immunotherapy.Frontiers in immunology · 2023Review
- Application of natural killer cells in pancreatic cancer.Oncology letters · 2021Review
- Parvovirus-Based Combinatorial Immunotherapy: A Reinforced Therapeutic Strategy against Poor-Prognosis Solid Cancers.Cancers · 2021Review
- Role of the Main Non HLA-Specific Activating NK Receptors in Pancreatic, Colorectal and Gastric Tumors Surveillance.Cancers · 2020Review
- The Immune Microenvironment in Pancreatic Cancer.International journal of molecular sciences · 2020Review
- The Oncoprotein SKI Acts as A Suppressor of NK Cell-Mediated Immunosurveillance in PDAC.Cancers · 2020Article
- An Immunological Glance on Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2020Review
- MiR-873, as a suppressor in cervical cancer, inhibits cells proliferation, invasion and migration via negatively regulating ULBP2.Genes & genomics · 2020Article
- NKG2D Ligand Shedding in Response to Stress: Role of ADAM10.Frontiers in immunology · 2020Review
- Cyr61/CCN1 targets for chemosensitization in pancreatic cancer.Oncotarget · 2019Article
- Targeting Immune-Related Molecules in Cancer Therapy: A ComprehensiveBioMed research international · 2019Article
- Natural Killer Cell Response to Chemotherapy-Stressed Cancer Cells: Role in Tumor Immunosurveillance.Frontiers in immunology · 2017Review
- Molecular docking investigation of calotropone as a potential natural therapeutic agent against pancreatic cancer.Journal of advanced pharmaceutical technology & researchArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to early onset of local invasion and distant metastasis, pancreatic cancer is the most lethal human malignant tumor, with a 5 year survival rate of less than 5%. As a effective chemotherapy drug for pancreatic cancer patients, gemcitabine is reported to inhibit cell proliferation as a nucleotide analog. In this study, we investigated the role of gemcitabine in immune regulation of pancreatic cancer. Our data showed that the level of soluble ULBP2 (sULBP2), a ligand of NKG2D receptor, decreased in the supernatants of pancreatic cancer cell lines when gemcitabine was added, and sULBP2 level correlated with NK92 cells cytotoxicity to pancreatic cancer cell lines. Importantly, our data showed that gemcitabine promoted PANC-1 cells and MIA PaCa-2 immune evasion by reducing ADAM10 expression, a metalloproteinase involved in sULBP2 shedding from cell membrane. Knockdown of ADAM10 clearly downregulated sULBP2 levels in the culture supernatants and cells became more susceptible to NK92 cytotoxicity. Serum samples and tumor samples were obtained from 45 patients with pancreatic ductal adenocarcinoma (PDAC). Statistical analysis showed a significant correlation between the serum level of sULBP2 with ADAM10 expression in PDAC tissues. In conclusion, our data demostrated that gemcitabine inhibits ULBP2 ectodomain shedding through the suppression of ADAM10 and enhance NK cells cytotoxicity by NKG2D-ULBP2 interaction. The results extends our understanding of gemcitabine in the treatment of pancreatic cancer from cell proliferation inhibition to immune regulation.
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