Evidence map›Paper›PMID 38729924›Full record

ArticleNature communications2024

Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.

Abdulla Berjis, Deeksha Muthumani, Oscar A Aguilar, Oz Pomp, Omar Johnson, Amanda V Finck, Nils W Engel, Linhui Chen, Nicolas Plachta, John Scholler and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

  1. Article
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  5. Review
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  9. Article
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  11. Article
  12. Article
  13. Review
  14. Article
  15. Innate immune cells in chimeric antigen receptor therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  16. Review
  17. Review
  18. Article
  19. Precision sniper for solid tumors: CAR-NK cell therapy.Cancer immunology, immunotherapy : CII · 2025
    Review
  20. Article
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

13 authors.

Abdulla BerjisCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Abdulla.Berjis@Pennmedicine.upenn.edu.ORCID http://orcid.org/0009-0007-7660-5611
Deeksha MuthumaniCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Oscar A AguilarDepartment of Microbiology and Immunology and Parker Institute of Cancer Immunotherapy, University of California; San Francisco, San Francisco, CA, USA.
Oz PompDepartment of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Omar JohnsonCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Amanda V FinckCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9595-8470
Nils W EngelCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Linhui ChenCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Nicolas PlachtaDepartment of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5035-7425
John SchollerCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Lewis L LanierDepartment of Microbiology and Immunology and Parker Institute of Cancer Immunotherapy, University of California; San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1308-3952
Carl H JuneCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0241-3557
Neil C SheppardCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. neil.sheppard@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-9551-9491

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DAVID A. MANKOFF · 1985 to 2026
$222.3M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Una T O'Doherty · 1999 to 2026
$78.6M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STOCK, PETER G · 2003 to 2019
$21.8M
NK MemoryR01AI068129 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANIER, LEWIS LEE · 2006 to 2020
$6.0M
Modeling Antibody-induced Immune Responses by NK cells in Mice and Humans (Resubmission 1)R01AI146581 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI DAS, JAYAJIT · 2020 to 2025
$2.3M
Modeling Antibody-induced Immune Responses by NK cells in Mice and HumansR56AI146581 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI DAS, JAYAJIT · 2019 to 2019
$512k
Cytek Aurora 5-Laser Spectral Flow CytometerS10OD026940 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SIMOES MARTINS BISPO, CLAUDIA · 2019 to 2019
$341k
NCI NIH HHS P30 CA016520NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI068129NIAID NIH HHS R01 AI146581NIAID NIH HHS R56 AI146581NIDDK NIH HHS P30 DK063720NIH HHS S10 OD026940
6 · The paper itself

Abstract

Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles. Pretreatment of NK cells with a combination of Interleukins-15 (IL-15) and IL-18 prior to cryopreservation improves NK cell recovery to ~90-100% and enables equal tumour control in a xenograft model of disseminated Raji cell lymphoma compared to non-cryopreserved NK cells. The mechanism of IL-15 and IL-18-induced protection incorporates two mechanisms: a transient reduction in intracellular granzyme B levels via degranulation, and the induction of antiapoptotic genes.

Indexed as

CryopreservationInterleukin-15Interleukin-18Killer Cells, NaturalAnimalsApoptosisCell Line, TumorCRISPR-Cas SystemsGranzymesHumansMiceGranzymesGZMB protein, humanIL15 protein, humanIL18 protein, humanInterleukin-15Interleukin-18

Identifiers

PMID38729924
PMCPMC11087472

What Socratic holds

Textmetadata
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 Socratic graph.