Evidence mapPaperPMID 40914422Full record

ArticleJournal of advanced research2026

Genetic manipulation of OGT enhances NK cell-mediated cytotoxicity in tumor immunity.

Se-Chan Oh, Bong Chan Jeon, In-Hwan Jang, Mi-Ran Song, Heeyoun Hwang, Dasom An, Liu Yue, Yuri Jung, Yunhee Lee, Seona Jo and 2 more

Abstract read
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

12 authors.

Se-Chan OhCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Bong Chan JeonInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
In-Hwan JangCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Mi-Ran SongInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Heeyoun HwangDigital OMICs Research Center, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
Dasom AnDigital OMICs Research Center, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
Liu YueInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Yuri JungInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Yunhee LeeImmunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Seona JoCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; KRIBB School of Advanced Bioconvergence, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
Sung-Kyun ParkInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea. Electronic address: skpark@kribb.re.kr.
Tae-Don KimCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; KRIBB School of Advanced Bioconvergence, University of Science and Technology (UST), Daejeon 34113, Republic of Korea; Department of Biopharmaceutical Convergence, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: tdkim@kribb.re.kr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionNatural killer (NK) cells are essential effectors in immune surveillance and cancer immunotherapy, but their function is often compromised by metabolic stress and environmental factors within the tumor microenvironment (TME). O-GlcNAcylation, a post-translational modification, regulates immune responses, yet its impact on NK cell function and therapeutic potential in immune cell-based therapies remains underexplored.

objectivesThis study investigates the effects of O-GlcNAcylation on NK cell-mediated cytotoxicity and its potential as a therapeutic target to enhance tumor immunity.

methodsWe investigated the impact of O-GlcNAcylation on NK cell cytotoxicity, focusing on its regulation under cytokine stimulation and pharmacological modulation. Mass spectrometry identified O-GlcNAc-modified proteins involved in NK cell cytotoxicity. NK92 cells were genetically engineered to delete the O-GlcNAc transferase (OGT) intronic splicing silencer (ISS) to ensure stable O-GlcNAcylation. The effects were evaluated under adverse TME conditions and in vivo tumor models. Gene expression analysis was performed to uncover the molecular networks underlying the observed effects.

resultsCytokine stimulation and the O-GlcNAcase (OGA) inhibitor Thiamet G increased O-GlcNAc levels, enhancing NK cell cytotoxicity. Proteomic analysis identified key O-GlcNAc-modified proteins, including NK cell regulators and LRPPRC, which modulate NK function. Genetically engineered NK92 cells lacking the OGT-ISS region exhibited stable O-GlcNAcylation, preserving potent cytotoxicity under tumor-mimicking conditions and superior tumor-killing activity in vivo. Whole-transcriptome analysis of OGT-ISS-deleted NK cells revealed downregulation of TGF-β signaling and upregulation of Type I interferon signaling, as well as genes involved in cell adhesion and mobility, suggesting enhanced target recognition and cytotoxic function of NK cells.

conclusionStabilization and enhancement of O-GlcNAcylation improve the target-killing capacity of NK cells while overcoming suppressive factors in the TME. These findings highlight advanced strategies, including genetic engineering of O-GlcNAc pathways, as potent approaches to augment NK-based immunotherapies against cancer.

Indexed as

Cytotoxicity, ImmunologicKiller Cells, NaturalN-AcetylglucosaminyltransferasesNeoplasmsAnimalsCell Line, TumorCytokinesHumansMiceProtein Processing, Post-TranslationalTumor MicroenvironmentCytokinesN-AcetylglucosaminyltransferasesO-GlcNAc transferaseCancer immunotherapyCytotoxicityNK cellO-GlcNAcylationOGT-ISS deletion

Identifiers

PMID40914422
PMCPMC13227225

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.