ArticleOncotarget2016
PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers.
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The trial behind it
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Who cites it
212 citing papers in PubMed, 290 citations in OpenAlex.
- Alterations in immune cell phenotype and cytotoxic capacity in HER2+ breast cancer patients receiving HER2-targeted neo-adjuvant therapy.British journal of cancer · 2023Trial
- Predicting Toxicity and Response to Pembrolizumab Through Germline Genomic HLA Class 1 Analysis.JNCI cancer spectrum · 2021Trial
- Increased Frequency of Dysfunctional Siglec-7Frontiers in immunology · 2021Trial
- PD-L1 Mediates Dysfunction in Activated PD-1Cancer immunology research · 2018Trial
- Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy.Pharmaceutical science advances · 2026Review
- Outcomes of Kaposi sarcoma in people living with HIV who maintain long-term viral suppression: A prospective case-series.HIV medicine · 2026Article
- PD-1-targeted IL-15 mutein activates CD8+ and CD4+ T cells in infection and cancer.JCI insight · 2026Article
- Peripheral blood immune cell subsets as non-invasive biomarkers of colorectal cancer stage, laterality, metastasis and survival.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy.Cell stem cell · 2026Review
- Altered natural killer cell function in children with severe malaria.ImmunoHorizons · 2026Article
- The multidimensional regulatory network of the PD‑1/PD‑L1 axis in the esophageal squamous cell carcinoma microenvironment: Implications for novel combination therapies and precision immunotherapy (Review).Oncology reports · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.Cancer communications (London, England) · 2026Review
- Programmed cell death-1: from a T-cell immune checkpoint to a regulator of Natural Killer cell biology.Frontiers in cell and developmental biology · 2026Review
- Article
- Overcoming NK cell resistance in triple-negative breast cancer via adcc with a humanized anti-CD147 antibody.Cancer immunology, immunotherapy : CII · 2025Article
- PD-1Journal of experimental & clinical cancer research : CR · 2025Article
- Article
- Precision enhancement of CAR-NK cells through non-viral engineering and highly multiplexed base editing.Journal for immunotherapy of cancer · 2025Article
152 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Programmed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T- and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD-1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56dimCD16pos NK cells with otherwise normal expression of NK surface receptors. PD-1pos NK cells from KS patients were hyporesponsive ex vivo following direct triggering of NKp30, NKp46 or CD16 activating receptors, or short stimulation with NK cell targets. PD-1pos NK cells failed to degranulate and release IFNγ, but exogenous IL-2 or IL-15 restored this defect. That PD-1 contributed to NK cell functional impairment and was not simply a marker of dysfunctional NK cells was confirmed in PD-1-transduced NKL cells. In vitro, PD-1 was induced at the surface of healthy control NK cells upon prolonged contact with cells expressing activating ligands, i.e. a condition mimicking persistent stimulation by tumor cells. Thus, PD-1 appears to plays a critical role in mediating NK cell exhaustion. The existence of this negative checkpoint fine-tuning NK activation highlights the possibility that manipulation of the PD-1 pathway may be a strategy for circumventing tumor escape not only from the T cell-, but also the NK-cell mediated immune surveillance.
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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.