Evidence map›Paper›PMID 42433369›Full record

ArticleFrontiers in immunology2026

Engineering with EP2/EP4 knockout and IL-15 transpresentation renders stem cell-derived NK cells self-persistent and resistant to PGE2 inhibition.

Marcos Vidal-Manrique, Laura Hooijmaijers, Julia A J Teders, Elif Saf, Kjell Klarenbeek, Iris M Hagemans, Jorge Cuenca-Escalona, Alessandra Cambi, I Jolanda M de Vries, Paul K J D de Jonge and 2 more

Erratum issuedAbstract read
In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Marcos Vidal-ManriqueDepartment of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Laura HooijmaijersDepartment of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Julia A J Teders *Department of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Elif Saf *Department of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Kjell Klarenbeek *Department of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Iris M HagemansDepartment of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Jorge Cuenca-EscalonaDepartment of Medical BioSciences, Radboud university medical center, Nijmegen, Netherlands.
Alessandra CambiDepartment of Medical BioSciences, Radboud university medical center, Nijmegen, Netherlands.
I Jolanda M de VriesDepartment of Medical BioSciences, Radboud university medical center, Nijmegen, Netherlands.
Paul K J D de JongeDepartment of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Anniek B van der WaartDepartment of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.
Harry DolstraDepartment of Laboratory Medicine, Laboratory of Hematology, Radboud university medical center, Nijmegen, Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adoptive Natural Killer (NK) cell transfer is a promising therapy for the treatment of cancer. We developed a GMP-compliant protocol to generate NK cells from hematopoietic stem and progenitor cells (HSPC-NK). However, the immunosuppressive tumor microenvironment - especially prostaglandin E2 (PGE2) signaling via E-prostanoid receptors EP2 and EP4- and lack of persistence of allogeneic NK cells hinders HSPC-NK therapeutic efficacy. Here, we enhanced the therapeutic efficacy of HSPC-NK cells by interfering with both EP2 and EP4 with antagonists or CRISPR-KO, and through engineering with IL-15 tethered to membrane-bound IL-15Rα (tIL15). We found that CRISPR interference of EP2 and EP4 fully rescued proliferation and potency of HSPC-NK cells under PGE2 rich conditions. In addition, combined EP2/EP4 KO and tIL15 engineering renders HSPC-NK cells resistant to PGE2, while improving their survival and functionality against different tumor targets in cytokine-deprived environments. Altogether, our EP2/EP4-KO tIL15-HSPC-NK cells pose a promising therapy for cancer.

Indexed as

DinoprostoneHematopoietic Stem CellsInterleukin-15Killer Cells, NaturalReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 SubtypeAnimalsGene Knockout TechniquesHumansMiceTumor MicroenvironmentDinoprostoneInterleukin-15Receptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 Subtypeadoptive cell transferCRISPRhematopoietic stem cellsIL-15 transpresentationNK cellsprostaglandin E2

Identifiers

PMID42433369
PMCPMC13350024

What Socratic holds

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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 Socratic graph.