ArticleThe Journal of allergy and clinical immunology2018
PD-1 blocks lytic granule polarization with concomitant impairment of integrin outside-in signaling in the natural killer cell immunological synapse.
Article in The Journal of allergy and clinical immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- Regulatory mechanisms of PD-1/PD-L1 in cancers.Molecular cancer · 2024Review
- Article
- Natural killer cells in pancreatic cancer stroma.World journal of gastroenterology · 2021Review
- Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future.Stem cell research & therapy · 2021Review
- Inability of granule polarization by NK cells defines tumor resistance and can be overcome by CAR or ADCC mediated targeting.Journal for immunotherapy of cancer · 2021Article
- Functional and metabolic targeting of natural killer cells to solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- Review
- Overview of Strategies to Improve Therapy against Tumors Using Natural Killer Cell.Journal of immunology research · 2020Review
- Boosting γδ T cell-mediated antibody-dependent cellular cytotoxicity by PD-1 blockade in follicular lymphoma.OncoimmunologyArticle
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundThe inhibitory receptor programmed cell death protein 1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic viral infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized.
objectiveWe sought to determine the effect of PD-1 signaling on NK cells.
methodsPD-1 was overexpressed in CD16-KHYG-1 (a human NK cell line with both antibody-dependent cellular cytotoxicity through CD16 and natural cytotoxicity through NKG2D) cells and stimulated by exposing the cells to NK-sensitive target cells expressing programmed death ligand 1 (PD-L1).
resultsPD-1 engagement by PD-L1 specifically blocked NK cell-mediated cytotoxicity without interfering with the conjugation between NK cells and target cells. Further examination showed that PD-1 signaling blocked lytic granule polarization in NK cells, which was accompanied by failure of integrin-linked kinase, a key molecule in the integrin outside-in signaling pathway, to accumulate in the immunological synapse after NK-target cell conjugation.
conclusionOur results suggest that NK cell cytotoxicity is inhibited by PD-1 engagement, which blocks lytic granule polarization to the NK cell immunological synapse with concomitant impairment of integrin outside-in signaling. This study provides novel mechanistic insights into how PD-1 inhibition disrupts NK cell function.
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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.