ArticleJournal of advanced research2026
Enhancement of NK cell activity via DNA-sensing inhibition by Poxin transgene.
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 2 papers.
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Who cites it
2 citing papers in PubMed.
- Unveiling the sensing potential of innate lymphoid cells.Communications biology · 2026Review
- Molecular mechanism of 2',3'-cGAMP degradation by monkeypox virus poxin-schlafen protein.The Journal of biological chemistry · 2026Article
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Authors and funding
11 authors.
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Abstract
introductionNatural Killer (NK) cell therapy has shown strong potential for cancer treatment; however, NK cell efficacy is limited by their short lifespan and suppression within the tumor microenvironment. One factor contributing to this suppression may be the activation of the cyclic GMP-AMP synthase (cGAS) pathway. Since the discovery of cGAS as a DNA sensor, there has been renewed interest in DNA sensing mechanisms, although the role of DNA sensing-mediated innate immune responses on NK cells remains unclear. Poxin, a protein derived from DNA viruses, is known to degrade the cGAS signaling product cyclic GMP-AMP (cGAMP) and could potentially alleviate DNA sensing-related stress in NK cells.
objectivesThis study aims to investigate whether Poxin expression can inhibit DNA sensing pathways in NK cells, thereby enhancing their cytotoxic function and anti-tumor activity.
methodsWe generated NK-92 cells expressing a Poxin transgene and evaluated their response to DNA sensing activation. The cGAS-STING pathway was stimulated through either exogenous plasmid transfection or irradiation to induce endogenous double-stranded DNA (dsDNA). We assessed NK-92 and umbilical cord blood derived primary NK (pNK) cells activity through cytotoxicity assay and analysis of perforin and granzyme B expression levels, performed RNA-seq analysis to explore the mechanism and conducted functional assays to evaluate anti-tumor efficacy of NK-92 and chimeric antigen receptors (CAR)-NK-92 cells.
resultsPoxin expression significantly inhibited the cGAS-STING pathway, reducing activation in response to both plasmid transfection and irradiation-induced dsDNA. RNA-seq analysis indicated increased levels of cytotoxic mediators, including perforin and granzyme B, in Poxin-expressing NK-92 cells. Furthermore, these transgenic NK-92/CAR-NK-92 cells exhibited enhanced anti-tumor activity compared to controls.
conclusionPoxin effectively suppresses DNA sensing-mediated innate immunity in NK cells, enhancing their cytotoxicity and anti-tumor effectiveness.
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