ArticleOncogene2017
Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers.
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Who cites it
245 citing papers in PubMed, 370 citations in OpenAlex.
- Dynamic transcriptional immune landscape in response to NK-cell therapy combined with gemcitabine plus S-1 in advanced pancreatic cancer: a phase 1b/2 trial.Signal transduction and targeted therapy · 2025Trial
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- First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.Signal transduction and targeted therapy · 2024Trial
- Trial
- Increased Frequency of Dysfunctional Siglec-7Frontiers in immunology · 2021Trial
- p38α orchestrates BRAFNature communications · 2026Article
- PD-1 regulates CD4Nature communications · 2026Article
- Identification and validation of programmed cell death-related genes in osteosarcoma: inhibiting CIB1 as a promising therapeutic strategy.BMC cancer · 2026Article
- Cracking the shield: oncolytic viruses versus the tumor-immune fortress.Cancer cell international · 2026Review
- PD-L1 Expression in Mesenchymal Stem/Stromal Cells: Impacts on Innate and Adaptive Immunity, Therapeutic Potential, and Biomarker Utility.International journal of molecular sciences · 2026Review
- An effective tumor-inhibiting siRNA delivery platform.Biochemical and biophysical research communications · 2026Article
- NK Cell Activation by Platinum Boosts Immunotherapy in HRAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Liver Transplantation Following Immune Checkpoint Inhibitor Therapy: What Do We Need to Know from Clinical and Immunological Perspective?International journal of molecular sciences · 2026Review
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Reprogramming the tumor immune microenvironment in cervical cancer: synergy between radiotherapy and immunotherapy.Molecular cancer · 2026Review
- Modelling Immune Dynamics in Locally Advanced MSI-H/dMMR Colorectal Cancer with Neoadjuvant Pembrolizumab Treatment: From Differential Equations to an Agent-Based Framework.Bulletin of mathematical biology · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Natural Killer Cells in Uterine Adenomyosis: Immunological Mechanisms and Therapeutic Perspectives.Journal of immunology research · 2026Review
- Cell death in sepsis: unveiling new perspectives on organ dysfunction.Frontiers in cell and developmental biology · 2026Review
- Novel therapeutic strategies for ccRCC through integration of systemic drug combinations and oncolytic adenovirus immunotherapy.Frontiers in immunology · 2026Article
185 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal expression of activating/inhibitory receptors leads to natural killer (NK) cells dysfunction in tumor. Here we show that programmed cell death protein 1 (PD-1), a well-known immune checkpoint of T cells, is highly expressed on peripheral and tumor-infiltrating NK cells from patients with digestive cancers including esophageal, liver, colorectal, gastric and biliary cancer. The increased PD-1 expression on NK cells indicates poorer survival in esophageal and liver cancers. Blocking PD-1/PD-L1 signaling markedly enhances cytokines production and degranulation and suppresses apoptosis of NK cells in vitro. PD-1/PD-L1 exerts inhibitory effect through repressing the activation of PI3K/AKT signaling in NK cells. More importantly, a PD-1 blocking antibody was found to significantly suppress the growth of xenografts in nude mice, and this inhibition of tumor growth was completely abrogated by NK depletion. These findings strongly suggested that PD-1 is an inhibitory regulator of NK cells in digestive cancers. PD-1 blockade might be an efficient strategy in NK cell-based tumor immunotherapy.
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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.