Evidence map›Paper›PMID 35119498›Full record

ArticleCancer immunology, immunotherapy : CII2022

Comparison of characteristics and tumor targeting properties of extracellular vesicles derived from primary NK cells or NK-cell lines stimulated with IL-15 or IL-12/15/18.

Miriam Aarsund, Filip M Segers, Yunjie Wu, Marit Inngjerdingen

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
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  14. NK-derived exosomes in anti-tumor strategies.Medical oncology (Northwood, London, England) · 2025
    Review
  15. Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Miriam AarsundDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Filip M SegersDepartment of Pharmacology, Clinic of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0001-8680-0751
Yunjie WuDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Marit InngjerdingenDepartment of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. mariti@medisin.uio.no.ORCID http://orcid.org/0000-0001-8965-661X
University of Oslo · NOOslo University Hospital · NO

Funding

Norges Forskningsråd 303256
6 · The paper itself

Abstract

NK cell-based therapies have shown promise for hematological cancer forms, but their use against solid tumors is hampered by their poor ability to infiltrate the tumor. NK cells release extracellular vesicles (EVs) containing cytolytic proteins, indicating that NK-cell derived EVs may have therapeutic potential. In this study, we compared the tumor-targeting potential of EVs derived from either primary NK cells or the NK cell lines NK-92 and KHYG-1 cultured in IL-15 alone or in combination with IL-12 and IL-18. Primary NK cells were also stimulated through the activating receptor CD16. Tumor cell apoptosis was measured using a panel of human colon, melanoma, glioblastoma, prostate, breast, and ovarian tumor cell line spheroids. NK cells or NK-92 cells stimulated with IL-12, IL-15, and IL-18 generated EVs with higher efficiency than EVs from resting cells, although similar amounts of EVs were produced under both conditions. Proteomic analysis indicated similar distribution of cytolytic proteins in EVs from primary NK cells and NK-92, but lower levels in KHYG-1 EVs that translated into poor capacity for KHYG-1 EVs at targeting tumor cell lines. Further, we show that CD16-stimulated NK cells release low amounts of EVs devoid of cytolytic proteins. Importantly, EVs from cytokine-stimulated NK cells penetrate into the spheroid core, and tumor spheroid susceptibility to NK-cell derived EVs was linked to differential expression of the NKG2D ligands MICA/B, which was blocked with an anti-NKG2D antibody. We conclude that EVs from activated primary NK cells or NK-92 cells has the best potential to infiltrate and target solid tumors.

Indexed as

Extracellular VesiclesInterleukin-12Interleukin-15Interleukin-18Killer Cells, NaturalCell Line, TumorHumansNeoplasmsNK Cell Lectin-Like Receptor Subfamily KProteomicsInterleukin-12Interleukin-15Interleukin-18NK Cell Lectin-Like Receptor Subfamily KEVsIL-12IL-15IL-18NK cellsNKG2D

Identifiers

PMID35119498
PMCPMC9374793
OpenAlexW4210768646

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.