Evidence map›Paper›PMID 34316033›Full record

ArticleCancer gene therapy2022

Cytokine-enhanced cytolytic activity of exosomes from NK Cells.

Yutaka Enomoto, Peng Li, Lisa M Jenkins, Dimitrios Anastasakis, Gaelyn C Lyons, Markus Hafner, Warren J Leonard

Open access · hybridAbstract read
In one paragraph

Article in Cancer gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
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  16. NK-derived exosomes in anti-tumor strategies.Medical oncology (Northwood, London, England) · 2025
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2 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 1 country.

Yutaka EnomotoLaboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA.
Peng LiLaboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA.
Lisa M JenkinsLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Dimitrios AnastasakisRNA Molecular Biology Group, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, 20892, USA.
Gaelyn C LyonsLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Markus HafnerRNA Molecular Biology Group, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-4336-6518
Warren J LeonardLaboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892-1674, USA. leonardw@nhlbi.nih.gov.ORCID http://orcid.org/0000-0002-5740-7448
National Institutes of Health · USNational Cancer Institute · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · US

Funding

IL-2 Family Cytokines and their Receptors-- Molecular Regulation via STATsZIAHL005402 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEONARD, WARREN J · 2009 to 2025
$26.8M
IL-2 Family Cytokines and their Receptors-- Biology of the IL-21 systemZIAHL005408 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEONARD, WARREN J · 2009 to 2025
$23.7M
IL-2 Family Cytokines and their Receptors-- Biology of the IL-2 systemZIAHL005401 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEONARD, WARREN J · 2009 to 2025
$22.5M
6 · The paper itself

Abstract

Natural killer (NK) cells play key roles in immune surveillance against tumors and viral infection. NK cells distinguish abnormal cells from healthy cells by cell-cell interaction with cell surface proteins and then attack target cells via multiple mechanisms. In addition, extracellular vesicles (EVs) derived from NK cells (NK-EVs), including exosomes, possess cytotoxic capacity against tumor cells, but their characteristics and regulation by cytokines remain unknown. Here, we report that EVs derived from human NK-92 cells stimulated with IL-15 + IL-21 show enhanced cytotoxic capacity against tumor cells. Major cytolytic granules, granzyme B and granzyme H, are enriched by IL-15 + IL-21 stimulation in NK-EVs; however, knockout experiments reveal those cytolytic granules are independent of enhanced cytotoxic capacity. To find out the key molecules, mass spectrometry analyses were performed with different cytokine conditions, no cytokine, IL-15, IL-21, or IL-15 + IL-21. We then found that CD226 (DNAM-1) on NK-EVs is enriched by IL-15 + IL-21 stimulation and that blocking antibodies against CD226 reduced the cytolytic activity of NK-EVs. We also show NK-EVs are taken up by target cells via macropinocytosis. Collectively, our findings elucidate the novel properties of NK-EVs and the mechanism of their incorporation into target cells.

Indexed as

ExosomesExtracellular VesiclesCytokinesCytotoxicity, ImmunologicHumansInterleukin-15Killer Cells, NaturalCytokinesInterleukin-15

Identifiers

PMID34316033
PMCPMC9209332
OpenAlexW3185591809

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.